rs777544121

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001387283.1(SMARCA4):c.1802C>A(p.Pro601Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P601L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SMARCA4
NM_001387283.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.43

Publications

3 publications found

Variant links:

Genes affected

SMARCA4 (HGNC:11100): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4) The protein encoded by this gene is a member of the SWI/SNF family of proteins and is similar to the brahma protein of Drosophila. 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 encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. In addition, this protein can bind BRCA1, as well as regulate the expression of the tumorigenic protein CD44. Mutations in this gene cause rhabdoid tumor predisposition syndrome type 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

SMARCA4 Gene-Disease associations (from GenCC):

Coffin-Siris syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Illumina
intellectual disability, autosomal dominant 16
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
rhabdoid tumor predisposition syndrome 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
uterine corpus sarcoma
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
familial rhabdoid tumor
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary nonpolyposis colon cancer
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

SMARCA4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35132134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1 link	c.1802C>A	p.Pro601Gln	missense_variant	Exon 11 of 36	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5 link	c.1802C>A	p.Pro601Gln	missense_variant	Exon 11 of 35	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SMARCA4	ENST00000646693.2 link	c.1802C>A	p.Pro601Gln	missense_variant	Exon 11 of 36		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10 link	c.1802C>A	p.Pro601Gln	missense_variant	Exon 11 of 35	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1 link	c.1802C>A	p.Pro601Gln	missense_variant	Exon 11 of 35			ENSP00000493975.1
SMARCA4	ENST00000541122.6 link	c.1802C>A	p.Pro601Gln	missense_variant	Exon 12 of 35	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1 link	c.1802C>A	p.Pro601Gln	missense_variant	Exon 11 of 34			ENSP00000496635.1
SMARCA4	ENST00000644737.1 link	c.1802C>A	p.Pro601Gln	missense_variant	Exon 11 of 34			ENSP00000495548.1
SMARCA4	ENST00000589677.5 link	c.1802C>A	p.Pro601Gln	missense_variant	Exon 12 of 35	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1 link	c.1214C>A	p.Pro405Gln	missense_variant	Exon 8 of 32			ENSP00000496004.1
SMARCA4	ENST00000644963.1 link	c.446C>A	p.Pro149Gln	missense_variant	Exon 4 of 28			ENSP00000495599.1
SMARCA4	ENST00000644065.1 link	c.527C>A	p.Pro176Gln	missense_variant	Exon 4 of 27			ENSP00000493615.1
SMARCA4	ENST00000642350.1 link	c.287C>A	p.Pro96Gln	missense_variant	Exon 3 of 27			ENSP00000495355.1
SMARCA4	ENST00000643857.1 link	c.155C>A	p.Pro52Gln	missense_variant	Exon 2 of 25			ENSP00000494159.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251496

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461810

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111944

Other (OTH)

AF:

0.00

AC:

AN:

60392

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

GnomAD4 genome

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.40

T;.;T;.;.;.;.;.;.;.;T;.;.;.;.;.;T;T;.;.;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.0

.;D;.;.;.;.;D;.;.;.;D;.;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.35

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.9

M;.;.;.;M;M;.;M;M;M;M;M;M;M;M;M;.;.;.;.;.

PhyloP100

7.4

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-2.0

N;.;.;.;.;.;.;.;.;.;N;.;N;.;N;.;.;N;.;.;.

REVEL

Benign

0.12

Sift

Benign

0.10

T;.;.;.;.;.;.;.;.;.;T;.;T;.;T;.;.;T;.;.;.

Sift4G

Benign

0.31

T;.;.;.;.;.;.;.;.;.;T;.;T;T;T;T;T;T;.;.;.

Vest4

0.70

ClinPred

0.81

GERP RS

4.8

PromoterAI

-0.013

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.8

Varity_R

0.11

gMVP

0.85

Mutation Taster

=23/77

disease causing

(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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over