NM_020159.5:c.902T>C

Variant names:

• chr4-94252628-T-C
• rs7439869
• NM_020159.5:c.902T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.58
• Publications: 41 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020159.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCAD1	NM_020159.5	MANE Select	c.902T>C	p.Val301Ala	missense	Exon 9 of 24	NP_064544.2
	SMARCAD1	NM_001128429.3		c.902T>C	p.Val301Ala	missense	Exon 9 of 24	NP_001121901.1
	SMARCAD1	NM_001128430.2		c.902T>C	p.Val301Ala	missense	Exon 9 of 24	NP_001121902.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCAD1	ENST00000354268.9	TSL:1 MANE Select	c.902T>C	p.Val301Ala	missense	Exon 9 of 24	ENSP00000346217.4
	SMARCAD1	ENST00000359052.8	TSL:1	c.902T>C	p.Val301Ala	missense	Exon 9 of 24	ENSP00000351947.4
	SMARCAD1	ENST00000457823.6	TSL:1	c.902T>C	p.Val301Ala	missense	Exon 9 of 24	ENSP00000415576.2

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105108 AN: 151948 Hom.: 37769 Cov.: 33

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

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.: 31 AF XY: 0.605 AC XY: 420843 AN XY: 695456

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

GnomAD4 genome AF: 0.692 AC: 105228 AN: 152066 Hom.: 37826 Cov.: 33 AF XY: 0.693 AC XY: 51499 AN XY: 74330

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

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

Submissions by phenotype

not provided Benign:2

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)

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	15
DANN	Benign	0.17
DEOGEN2	Benign	0.069	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.055	T
MetaRNN	Benign	5.6e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.81	N
PhyloP100		1.6
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.68	N
REVEL	Benign	0.070
Sift	Benign	1.0	T
Sift4G	Benign	0.81	T
Polyphen		0.0	B
Vest4		0.020
MPC		0.36
ClinPred		0.0023	T
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)

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

Other links and lift over

dbSNP: rs7439869; hg19: chr4-95173779; COSMIC: COSV62772953; COSMIC: COSV62772953;