rs1555797492

Variant names:

• chr19-11061814-T-TGAGCCCCGACATTCCAGTCTCGACCCC
• rs1555797492
• NM_001387283.1:c.*6_*32dupGACATTCCAGTCTCGACCCCGAGCCCC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003072.5(SMARCA4):​c.*6_*32dupGACATTCCAGTCTCGACCCCGAGCCCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMARCA4 NM_003072.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.16

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.*6_*32dupGACATTCCAGTCTCGACCCCGAGCCCC		3_prime_UTR_variant	Exon 36 of 36	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.*6_*32dupGACATTCCAGTCTCGACCCCGAGCCCC		3_prime_UTR_variant	Exon 35 of 35	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.*6_*32dupGACATTCCAGTCTCGACCCCGAGCCCC		3_prime_UTR_variant	Exon 36 of 36		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.*6_*32dupGACATTCCAGTCTCGACCCCGAGCCCC		3_prime_UTR_variant	Exon 35 of 35	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.*6_*32dupGACATTCCAGTCTCGACCCCGAGCCCC		3_prime_UTR_variant	Exon 35 of 35			ENSP00000493975.1
SMARCA4	ENST00000643296.1	c.*6_*32dupGACATTCCAGTCTCGACCCCGAGCCCC		3_prime_UTR_variant	Exon 34 of 34			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.*6_*32dupGACATTCCAGTCTCGACCCCGAGCCCC		3_prime_UTR_variant	Exon 34 of 34			ENSP00000495548.1
SMARCA4	ENST00000643995.1	c.*6_*32dupGACATTCCAGTCTCGACCCCGAGCCCC		3_prime_UTR_variant	Exon 32 of 32			ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.*6_*32dupGACATTCCAGTCTCGACCCCGAGCCCC		3_prime_UTR_variant	Exon 28 of 28			ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.*6_*32dupGACATTCCAGTCTCGACCCCGAGCCCC		3_prime_UTR_variant	Exon 27 of 27			ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.*6_*32dupGACATTCCAGTCTCGACCCCGAGCCCC		3_prime_UTR_variant	Exon 27 of 27			ENSP00000495355.1
SMARCA4	ENST00000643857.1	c.*6_*32dupGACATTCCAGTCTCGACCCCGAGCCCC		3_prime_UTR_variant	Exon 25 of 25			ENSP00000494159.1
SMARCA4	ENST00000538456.4	c.*6_*32dupGACATTCCAGTCTCGACCCCGAGCCCC		3_prime_UTR_variant	Exon 8 of 8	3		ENSP00000495197.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rhabdoid tumor predisposition syndrome 2 Uncertain:1

Jul 16, 2016

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555797492; hg19: chr19-11172490;