4-143514085-C-T

Position:

chr4-143514085-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2

The NM_003601.4(SMARCA5):c.161C>T(p.Ala54Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000435 in 1,553,136 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00044 ( 2 hom. )

Consequence

SMARCA5
NM_003601.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.592

Variant links:

Genes affected

SMARCA5 (HGNC:11101): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 5) The protein encoded by this gene is a member of the SWI/SNF family of proteins. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The protein encoded by this gene is a component of the chromatin remodeling and spacing factor RSF, a facilitator of the transcription of class II genes by RNA polymerase II. The encoded protein is similar in sequence to the Drosophila ISWI chromatin remodeling protein. [provided by RefSeq, Jul 2008]

SMARCA5 links:

SMARCA5-AS1 (HGNC:):

SMARCA5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SMARCA5. . Gene score misZ 5.418 (greater than the threshold 3.09). Trascript score misZ 4.0452 (greater than threshold 3.09). GenCC has associacion of gene with complex neurodevelopmental disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.008321255).

BP6

Variant 4-143514085-C-T is Benign according to our data. Variant chr4-143514085-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3048543.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 62 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA5	NM_003601.4 linkuse as main transcript	c.161C>T	p.Ala54Val	missense_variant	1/24	ENST00000283131.4	NP_003592.3	O60264
SMARCA5	XM_047416323.1 linkuse as main transcript	c.161C>T	p.Ala54Val	missense_variant	1/14		XP_047272279.1
SMARCA5-AS1	NR_104027.1 linkuse as main transcript	n.534G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA5	ENST00000283131.4 linkuse as main transcript	c.161C>T	p.Ala54Val	missense_variant	1/24	1	NM_003601.4	ENSP00000283131.3		O60264
SMARCA5-AS1	ENST00000500800.2 linkuse as main transcript	n.332G>A		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes

AF:

0.000407

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000549

AC:

AN:

156676

Hom.:

AF XY:

0.000695

AC XY:

AN XY:

87810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000191

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00160

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000561

Gnomad OTH exome

AF:

0.000931

GnomAD4 exome

AF:

0.000438

AC:

614

AN:

1400818

Hom.:

Cov.:

AF XY:

0.000472

AC XY:

327

AN XY:

693306

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000237

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00111

Gnomad4 FIN exome

AF:

0.0000289

Gnomad4 NFE exome

AF:

0.000440

Gnomad4 OTH exome

AF:

0.000429

GnomAD4 genome

AF:

0.000407

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000416

Hom.:

Bravo

AF:

0.000348

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000515

AC:

ExAC

AF:

0.000504

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SMARCA5-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 09, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.23

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0082

LIST_S2

Benign

0.64

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.0083

MetaSVM

Benign

-0.65

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.26

REVEL

Benign

0.083

Sift

Benign

0.38

Sift4G

Benign

0.33

Polyphen

0.056

Vest4

0.13

MVP

0.38

MPC

0.21

ClinPred

0.015

GERP RS

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.047

gMVP

0.27

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