NM_020159.5:c.*925T>C

Variant names:

• chr4-94290459-T-C
• rs8336
• NM_020159.5:c.*925T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020159.5(SMARCAD1):​c.*925T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 454,208 control chromosomes in the GnomAD database, including 81,785 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.57 (25034 hom., cov: 32)
  • Exomes 𝑓: 0.61 (56751 hom.)
• Consequence: SMARCAD1 NM_020159.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCAD1	NM_020159.5	c.*925T>C		3_prime_UTR_variant	Exon 24 of 24	ENST00000354268.9	NP_064544.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCAD1	ENST00000354268.9	c.*925T>C		3_prime_UTR_variant	Exon 24 of 24	1	NM_020159.5	ENSP00000346217.4
SMARCAD1	ENST00000359052.8	c.*925T>C		3_prime_UTR_variant	Exon 24 of 24	1		ENSP00000351947.4
SMARCAD1	ENST00000457823.6	c.*925T>C		3_prime_UTR_variant	Exon 24 of 24	1		ENSP00000415576.2

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86846 AN: 151896 Hom.: 25012 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.559

GnomAD2 exomes AF: 0.620 AC: 84352 AN: 136028 AF XY: 0.617

Gnomad AFR exome AF: 0.491

Gnomad AMR exome AF: 0.725

Gnomad ASJ exome AF: 0.533

Gnomad EAS exome AF: 0.708

Gnomad FIN exome AF: 0.563

Gnomad NFE exome AF: 0.586

Gnomad OTH exome AF: 0.589

GnomAD4 exome AF: 0.609 AC: 184089 AN: 302192 Hom.: 56751 Cov.: 0 AF XY: 0.610 AC XY: 105082 AN XY: 172242

African (AFR) AF: 0.501 AC: 4284 AN: 8550

American (AMR) AF: 0.726 AC: 19801 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 5722 AN: 10784

East Asian (EAS) AF: 0.723 AC: 6655 AN: 9210

South Asian (SAS) AF: 0.631 AC: 37656 AN: 59646

European-Finnish (FIN) AF: 0.570 AC: 7283 AN: 12774

Middle Eastern (MID) AF: 0.555 AC: 638 AN: 1150

European-Non Finnish (NFE) AF: 0.590 AC: 93702 AN: 158760

Other (OTH) AF: 0.594 AC: 8348 AN: 14044

GnomAD4 genome AF: 0.572 AC: 86918 AN: 152016 Hom.: 25034 Cov.: 32 AF XY: 0.577 AC XY: 42877 AN XY: 74312

African (AFR) AF: 0.498 AC: 20665 AN: 41476

American (AMR) AF: 0.641 AC: 9790 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1854 AN: 3468

East Asian (EAS) AF: 0.718 AC: 3709 AN: 5164

South Asian (SAS) AF: 0.636 AC: 3073 AN: 4828

European-Finnish (FIN) AF: 0.572 AC: 6036 AN: 10546

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.587 AC: 39859 AN: 67948

Other (OTH) AF: 0.565 AC: 1194 AN: 2112

Alfa AF: 0.585 Hom.: 100790

Bravo AF: 0.573

Asia WGS AF: 0.679 AC: 2363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs8336; hg19: chr4-95211610;