Genetic Variant NM_020159.5:c.154G>A (chr4-94208548-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_020159.5(SMARCAD1):c.154G>A(p.Ala52Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000428 in 1,614,028 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 3 hom. )

Consequence

SMARCAD1
NM_020159.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.24

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004745841).

BP6

Variant 4-94208548-G-A is Benign according to our data. Variant chr4-94208548-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3771225.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00211 (321/152180) while in subpopulation AFR AF= 0.0072 (299/41502). AF 95% confidence interval is 0.00653. There are 1 homozygotes in gnomad4. There are 154 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 321 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCAD1	NM_020159.5 link	c.154G>A	p.Ala52Thr	missense_variant	Exon 2 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.154G>A	p.Ala52Thr	missense_variant	Exon 2 of 24	1	NM_020159.5	ENSP00000346217.4		Q9H4L7-1

Frequencies

GnomAD3 genomes

AF:

0.00210

AC:

319

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00718

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000553

AC:

139

AN:

251472

Hom.:

AF XY:

0.000412

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00701

Gnomad AMR exome

AF:

0.000491

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000527

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000253

AC:

370

AN:

1461848

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

143

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00756

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000531

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.00211

AC:

321

AN:

152180

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

154

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00720

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000446

Hom.:

Bravo

AF:

0.00228

ESP6500AA

AF:

0.00749

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000717

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SMARCAD1: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.087

.;.;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.070

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.82

.;T;T

M_CAP

Benign

0.0097

MetaRNN

Benign

0.0047

T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.55

N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.30

N;N;N

REVEL

Benign

0.072

Sift

Benign

0.090

T;T;T

Sift4G

Benign

0.19

T;T;T

Polyphen

0.59

P;P;P

Vest4

0.18

MVP

0.26

MPC

0.32

ClinPred

0.026

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.086

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