rs11722476

Positions:

chr4-94249688-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_020159.5(SMARCAD1):c.740G>A(p.Ser247Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,602,518 control chromosomes in the GnomAD database, including 148,090 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.38 ( 11860 hom., cov: 31)

Exomes 𝑓: 0.42 ( 136230 hom. )

Consequence

SMARCAD1
NM_020159.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.176

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 links:

SMARCAD1 (HGNC:):

SMARCAD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SMARCAD1. . Gene score misZ 3.492 (greater than the threshold 3.09). Trascript score misZ 4.2048 (greater than threshold 3.09). GenCC has associacion of gene with absence of fingerprints-congenital milia syndrome, ectodermal dysplasia syndrome, isolated congenital adermatoglyphia, palmoplantar keratoderma-sclerodactyly syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=1.8179811E-6).

BP6

Variant 4-94249688-G-A is Benign according to our data. Variant chr4-94249688-G-A is described in ClinVar as [Benign]. Clinvar id is 1286948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-94249688-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCAD1	NM_020159.5 linkuse as main transcript	c.740G>A	p.Ser247Asn	missense_variant	7/24	ENST00000354268.9	NP_064544.2	Q9H4L7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCAD1	ENST00000354268.9 linkuse as main transcript	c.740G>A	p.Ser247Asn	missense_variant	7/24	1	NM_020159.5	ENSP00000346217.4		Q9H4L7-1

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57383

AN:

151356

Hom.:

11840

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.417

Gnomad AMR

AF:

0.480

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.715

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.387

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.367

GnomAD3 exomes

AF:

0.467

AC:

117053

AN:

250898

Hom.:

29521

AF XY:

0.466

AC XY:

63242

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.235

Gnomad AMR exome

AF:

0.636

Gnomad ASJ exome

AF:

0.394

Gnomad EAS exome

AF:

0.708

Gnomad SAS exome

AF:

0.581

Gnomad FIN exome

AF:

0.393

Gnomad NFE exome

AF:

0.401

Gnomad OTH exome

AF:

0.428

GnomAD4 exome

AF:

0.423

AC:

613556

AN:

1451044

Hom.:

136230

Cov.:

AF XY:

0.427

AC XY:

308711

AN XY:

722566

show subpopulations

Gnomad4 AFR exome

AF:

0.229

Gnomad4 AMR exome

AF:

0.620

Gnomad4 ASJ exome

AF:

0.391

Gnomad4 EAS exome

AF:

0.756

Gnomad4 SAS exome

AF:

0.576

Gnomad4 FIN exome

AF:

0.391

Gnomad4 NFE exome

AF:

0.400

Gnomad4 OTH exome

AF:

0.414

GnomAD4 genome

AF:

0.379

AC:

57412

AN:

151474

Hom.:

11860

Cov.:

AF XY:

0.387

AC XY:

28612

AN XY:

73974

show subpopulations

Gnomad4 AFR

AF:

0.243

Gnomad4 AMR

AF:

0.482

Gnomad4 ASJ

AF:

0.381

Gnomad4 EAS

AF:

0.715

Gnomad4 SAS

AF:

0.588

Gnomad4 FIN

AF:

0.387

Gnomad4 NFE

AF:

0.397

Gnomad4 OTH

AF:

0.374

Alfa

AF:

0.404

Hom.:

31926

Bravo

AF:

0.382

TwinsUK

AF:

0.394

AC:

1462

ALSPAC

AF:

0.398

AC:

1533

ESP6500AA

AF:

0.243

AC:

1071

ESP6500EA

AF:

0.390

AC:

3353

ExAC

AF:

0.456

AC:

55327

Asia WGS

AF:

0.628

AC:

2179

AN:

3468

EpiCase

AF:

0.387

EpiControl

AF:

0.394

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 22864933) -

Keratoderma with scleroatrophy of the extremities

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Basan syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Adermatoglyphia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.13

.;.;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.58

.;T;T

MetaRNN

Benign

0.0000018

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.74

N;N;N

REVEL

Benign

0.20

Sift

Benign

0.50

T;T;T

Sift4G

Benign

0.49

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.033

MPC

0.28

ClinPred

0.0033

GERP RS

0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.046

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over