dbSNP rs1114167276: SMARCAD1:c.1281+666T>C (chr4-94253673-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_020159.5(SMARCAD1):c.1281+666T>C variant causes a intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SMARCAD1
NM_020159.5 intron

Scores

Splicing: ADA: 0.2554

Clinical Significance

Pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 5.04

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 4-94253673-T-C is Pathogenic according to our data. Variant chr4-94253673-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 187777.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCAD1	NM_020159.5 link	c.1281+666T>C		intron_variant	Intron 9 of 23	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.1281+666T>C		intron_variant	Intron 9 of 23	1	NM_020159.5	ENSP00000346217.4		Q9H4L7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

855500

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

396564

African (AFR)

AF:

0.00

AC:

AN:

16046

American (AMR)

AF:

0.00

AC:

AN:

3942

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5558

East Asian (EAS)

AF:

0.00

AC:

AN:

4870

South Asian (SAS)

AF:

0.00

AC:

AN:

19790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

962

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1658

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

774368

Other (OTH)

AF:

0.00

AC:

AN:

28306

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Keratoderma with scleroatrophy of the extremities

Pathogenic:1

Dec 01, 2014

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Adermatoglyphia

Pathogenic:1

Dec 01, 2014

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

0.99

PhyloP100

5.0

PromoterAI

-0.19

Neutral

(source)

Mutation Taster

=3/97

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.26

dbscSNV1_RF

Benign

0.48

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over