Genetic Variant SMARCA5:p.Ser47Phe (chr4-143514064-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003601.4(SMARCA5):c.140C>T(p.Ser47Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,942 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S47C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SMARCA5
NM_003601.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.314

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14501593).

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.140C>T	p.Ser47Phe	missense	Exon 1 of 24	NP_003592.3
	SMARCA5-AS1	NR_104027.1		n.555G>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.140C>T	p.Ser47Phe	missense	Exon 1 of 24	ENSP00000283131.3	O60264
SMARCA5-AS1	ENST00000500800.3	TSL:1	n.353G>A		non_coding_transcript_exon	Exon 2 of 2
SMARCA5	ENST00000940952.1		c.140C>T	p.Ser47Phe	missense	Exon 1 of 25	ENSP00000611011.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000606

AC:

AN:

165038

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000762

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000214

AC:

AN:

1399942

Hom.:

Cov.:

AF XY:

0.00000288

AC XY:

AN XY:

694094

show subpopulations

African (AFR)

AF:

0.0000315

AC:

AN:

31732

American (AMR)

AF:

0.00

AC:

AN:

39258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24904

East Asian (EAS)

AF:

0.0000271

AC:

AN:

36928

South Asian (SAS)

AF:

0.00

AC:

AN:

82158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5626

European-Non Finnish (NFE)

AF:

9.18e-7

AC:

AN:

1089592

Other (OTH)

AF:

0.00

AC:

AN:

58126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.38

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.54

MutationAssessor

Benign

0.0

PhyloP100

-0.31

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.3

REVEL

Benign

0.13

Sift

Benign

0.059

Sift4G

Uncertain

0.037

Polyphen

0.025

Vest4

0.14

MutPred

0.34

Loss of glycosylation at S47 (P = 0.006)

MVP

0.29

MPC

0.23

ClinPred

0.063

GERP RS

2.0

PromoterAI

-0.035

Neutral

(source)

Varity_R

0.068

gMVP

0.32

Mutation Taster

=98/2

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