Genetic Variant SMARCA5:p.Ala5Ser (chr4-143513937-G-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.13G>T(p.Ala5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,545,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SMARCA5
NM_003601.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.619

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:

Genome browser will be placed here

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=0.08778763).

BS2

High AC in GnomAdExome4 at 15 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.13G>T	p.Ala5Ser	missense	Exon 1 of 24	NP_003592.3
	SMARCA5-AS1	NR_104027.1		n.682C>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.13G>T	p.Ala5Ser	missense	Exon 1 of 24	ENSP00000283131.3	O60264
SMARCA5-AS1	ENST00000500800.3	TSL:1	n.480C>A		non_coding_transcript_exon	Exon 2 of 2
SMARCA5	ENST00000940952.1		c.13G>T	p.Ala5Ser	missense	Exon 1 of 25	ENSP00000611011.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000699

AC:

AN:

143136

AF XY:

0.0000127

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000379

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000108

AC:

AN:

1393306

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

688874

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31610

American (AMR)

AF:

0.000132

AC:

AN:

37744

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25186

East Asian (EAS)

AF:

0.00

AC:

AN:

36122

South Asian (SAS)

AF:

0.0000125

AC:

AN:

80188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33978

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5522

European-Non Finnish (NFE)

AF:

0.00000830

AC:

AN:

1084750

Other (OTH)

AF:

0.00

AC:

AN:

58206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

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

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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

-0.026

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.26

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.67

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.088

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.0

PhyloP100

0.62

PrimateAI

Uncertain

0.78

PROVEAN

Benign

0.16

REVEL

Benign

0.20

Sift

Benign

0.72

Sift4G

Benign

0.67

Polyphen

0.0060

Vest4

0.19

MutPred

0.21

Gain of phosphorylation at E5 (P = 6e-04)

MVP

0.41

MPC

0.19

ClinPred

0.15

GERP RS

3.4

PromoterAI

-0.10

Neutral

(source)

Varity_R

0.082

gMVP

0.38

Mutation Taster

=96/4

polymorphism

(source)

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

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