Genetic Variant SMARCA5:p.Ala44Val (chr4-143514055-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003601.4(SMARCA5):c.131C>T(p.Ala44Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000568 in 1,407,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

SMARCA5
NM_003601.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.579

Publications

0 publications found

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:39982): (SMARCA5 antisense RNA 1)

SMARCA5-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13404414).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003601.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCA5	NM_003601.4	MANE Select	c.131C>T	p.Ala44Val	missense	Exon 1 of 24	NP_003592.3
	SMARCA5-AS1	NR_104027.1		n.564G>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMARCA5	ENST00000283131.4	TSL:1 MANE Select	c.131C>T	p.Ala44Val	missense	Exon 1 of 24	ENSP00000283131.3	O60264
SMARCA5-AS1	ENST00000500800.3	TSL:1	n.362G>A		non_coding_transcript_exon	Exon 2 of 2
SMARCA5	ENST00000940952.1		c.131C>T	p.Ala44Val	missense	Exon 1 of 25	ENSP00000611011.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000568

AC:

AN:

1407746

Hom.:

Cov.:

AF XY:

0.00000860

AC XY:

AN XY:

697350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31930

American (AMR)

AF:

0.00

AC:

AN:

39238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25236

East Asian (EAS)

AF:

0.00

AC:

AN:

37198

South Asian (SAS)

AF:

0.00

AC:

AN:

82082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

0.00000732

AC:

AN:

1093492

Other (OTH)

AF:

0.00

AC:

AN:

58690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.00065

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.61

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.52

MutationAssessor

Benign

0.0

PhyloP100

0.58

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.43

REVEL

Benign

0.19

Sift

Benign

0.21

Sift4G

Benign

0.38

Polyphen

0.0090

Vest4

0.18

MutPred

0.26

Loss of phosphorylation at S47 (P = 0.157)

MVP

0.42

MPC

0.21

ClinPred

0.22

GERP RS

3.2

PromoterAI

-0.16

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.083

gMVP

0.36

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over