rs6919

Variant names:

• chr17-63832125-T-A
• rs6919
• NM_001098426.2:c.*813A>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098426.2(SMARCD2):​c.*813A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 788,718 control chromosomes in the GnomAD database, including 166,553 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.69 (37798 hom., cov: 34)
  • Exomes 𝑓: 0.63 (128755 hom.)
• Consequence: SMARCD2 NM_001098426.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.844

Genes affected

SMARCD2 (HGNC:11107): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 2) The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which 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 and has sequence similarity to the yeast Swp73 protein. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PSMC5 (HGNC:9552): (proteasome 26S subunit, ATPase 5) The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes one of the ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. In addition to participation in proteasome functions, this subunit may participate in transcriptional regulation since it has been shown to interact with the thyroid hormone receptor and retinoid X receptor-alpha. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCD2	NM_001098426.2	c.*813A>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000448276.7	NP_001091896.1
PSMC5	NM_002805.6	c.*156T>A		downstream_gene_variant		ENST00000310144.11	NP_002796.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCD2	ENST00000448276	c.*813A>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_001098426.2	ENSP00000392617.2
PSMC5	ENST00000310144.11	c.*156T>A		downstream_gene_variant		1	NM_002805.6	ENSP00000310572.6

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105401 AN: 152080 Hom.: 37739 Cov.: 34

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.653

GnomAD4 exome AF: 0.632 AC: 401979 AN: 636520 Hom.: 128755 Cov.: 8 AF XY: 0.634 AC XY: 210067 AN XY: 331100

Gnomad4 AFR exome AF: 0.899

Gnomad4 AMR exome AF: 0.632

Gnomad4 ASJ exome AF: 0.525

Gnomad4 EAS exome AF: 0.594

Gnomad4 SAS exome AF: 0.738

Gnomad4 FIN exome AF: 0.650

Gnomad4 NFE exome AF: 0.614

Gnomad4 OTH exome AF: 0.624

GnomAD4 genome AF: 0.693 AC: 105516 AN: 152198 Hom.: 37798 Cov.: 34 AF XY: 0.693 AC XY: 51605 AN XY: 74414

Gnomad4 AFR AF: 0.893

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.748

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.651

Alfa AF: 0.662 Hom.: 4228

Bravo AF: 0.697

Asia WGS AF: 0.685 AC: 2382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.80
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2

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

LitVar

Other links and lift over

dbSNP: rs6919; hg19: chr17-61909485; COSMIC: COSV56739516; COSMIC: COSV56739516;