rs7439869

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020159.5(SMARCAD1):c.902T>C(p.Val301Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 1,554,320 control chromosomes in the GnomAD database, including 298,631 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 37826 hom., cov: 33)

Exomes 𝑓: 0.61 ( 260805 hom. )

Consequence

SMARCAD1
NM_020159.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.58

Publications

41 publications found

Variant links:

Genes affected

SMARCAD1 (HGNC:18398): (SWI/SNF-related, matrix-associated actin-dependent regulator of chromatin, subfamily a, containing DEAD/H box 1) This gene encodes a member of the SNF subfamily of helicase proteins. The encoded protein plays a critical role in the restoration of heterochromatin organization and propagation of epigenetic patterns following DNA replication by mediating histone H3/H4 deacetylation. Mutations in this gene are associated with adermatoglyphia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

SMARCAD1 Gene-Disease associations (from GenCC):

ectodermal dysplasia syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina
isolated congenital adermatoglyphia
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
palmoplantar keratoderma-sclerodactyly syndrome
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet
absence of fingerprints-congenital milia syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SMARCAD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.577926E-7).

BP6

Variant 4-94252628-T-C is Benign according to our data. Variant chr4-94252628-T-C is described in ClinVar as Benign. ClinVar VariationId is 1220932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCAD1	NM_020159.5 link	c.902T>C	p.Val301Ala	missense_variant	Exon 9 of 24	ENST00000354268.9	NP_064544.2	Q9H4L7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCAD1	ENST00000354268.9 link	c.902T>C	p.Val301Ala	missense_variant	Exon 9 of 24	1	NM_020159.5	ENSP00000346217.4		Q9H4L7-1

Frequencies

GnomAD3 genomes

AF:

0.692

AC:

105108

AN:

151948

Hom.:

37769

Cov.:

show subpopulations

Gnomad AFR

AF:

0.907

Gnomad AMI

AF:

0.613

Gnomad AMR

AF:

0.689

Gnomad ASJ

AF:

0.564

Gnomad EAS

AF:

0.718

Gnomad SAS

AF:

0.645

Gnomad FIN

AF:

0.572

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.590

Gnomad OTH

AF:

0.648

GnomAD2 exomes

AF:

0.638

AC:

125256

AN:

196308

AF XY:

0.628

show subpopulations

Gnomad AFR exome

AF:

0.913

Gnomad AMR exome

AF:

0.736

Gnomad ASJ exome

AF:

0.554

Gnomad EAS exome

AF:

0.709

Gnomad FIN exome

AF:

0.578

Gnomad NFE exome

AF:

0.580

Gnomad OTH exome

AF:

0.606

GnomAD4 exome

AF:

0.606

AC:

849279

AN:

1402254

Hom.:

260805

Cov.:

AF XY:

0.605

AC XY:

420843

AN XY:

695456

show subpopulations

African (AFR)

AF:

0.919

AC:

28098

AN:

30582

American (AMR)

AF:

0.732

AC:

24887

AN:

34006

Ashkenazi Jewish (ASJ)

AF:

0.557

AC:

13369

AN:

24004

East Asian (EAS)

AF:

0.759

AC:

29487

AN:

38826

South Asian (SAS)

AF:

0.641

AC:

49598

AN:

77356

European-Finnish (FIN)

AF:

0.577

AC:

29620

AN:

51358

Middle Eastern (MID)

AF:

0.616

AC:

3416

AN:

5544

European-Non Finnish (NFE)

AF:

0.587

AC:

635112

AN:

1082762

Other (OTH)

AF:

0.617

AC:

35692

AN:

57816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

13946

27891

41837

55782

69728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17736

35472

53208

70944

88680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.692

AC:

105228

AN:

152066

Hom.:

37826

Cov.:

AF XY:

0.693

AC XY:

51499

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.907

AC:

37656

AN:

41534

American (AMR)

AF:

0.690

AC:

10526

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

1958

AN:

3470

East Asian (EAS)

AF:

0.718

AC:

3715

AN:

5176

South Asian (SAS)

AF:

0.644

AC:

3107

AN:

4822

European-Finnish (FIN)

AF:

0.572

AC:

6017

AN:

10528

Middle Eastern (MID)

AF:

0.643

AC:

189

AN:

294

European-Non Finnish (NFE)

AF:

0.590

AC:

40120

AN:

67952

Other (OTH)

AF:

0.654

AC:

1381

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1523

3047

4570

6094

7617

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.622

Hom.:

92495

Bravo

AF:

0.712

TwinsUK

AF:

0.581

AC:

2153

ALSPAC

AF:

0.573

AC:

2207

ESP6500AA

AF:

0.909

AC:

3962

ESP6500EA

AF:

0.596

AC:

5093

ExAC

AF:

0.627

AC:

75263

Asia WGS

AF:

0.701

AC:

2434

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 29874175) -

Keratoderma with scleroatrophy of the extremities

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Basan syndrome

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Adermatoglyphia

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.17

DEOGEN2

Benign

0.069

.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.055

.;T;T

MetaRNN

Benign

5.6e-7

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

N;N;N

PhyloP100

1.6

PrimateAI

Benign

0.31

PROVEAN

Benign

0.68

N;N;N

REVEL

Benign

0.070

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.81

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.020

MPC

0.36

ClinPred

0.0023

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.017

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over