chr17-63832125-T-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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]

PSMC5 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098426.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCD2	NM_001098426.2	MANE Select	c.*813A>T		3_prime_UTR	Exon 13 of 13	NP_001091896.1
	SMARCD2	NM_001330440.2		c.*813A>T		3_prime_UTR	Exon 13 of 13	NP_001317369.1
	SMARCD2	NM_001330439.1		c.*813A>T		3_prime_UTR	Exon 13 of 13	NP_001317368.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCD2	ENST00000448276.7	TSL:1 MANE Select	c.*813A>T		3_prime_UTR	Exon 13 of 13	ENSP00000392617.2
	SMARCD2	ENST00000697953.1		n.3261A>T		non_coding_transcript_exon	Exon 10 of 10
	SMARCD2	ENST00000698013.1		n.3373A>T		non_coding_transcript_exon	Exon 8 of 8

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

African (AFR) AF: 0.899 AC: 14867 AN: 16546

American (AMR) AF: 0.632 AC: 17761 AN: 28108

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 8661 AN: 16496

East Asian (EAS) AF: 0.594 AC: 19076 AN: 32110

South Asian (SAS) AF: 0.738 AC: 39559 AN: 53588

European-Finnish (FIN) AF: 0.650 AC: 22678 AN: 34910

Middle Eastern (MID) AF: 0.617 AC: 1554 AN: 2520

European-Non Finnish (NFE) AF: 0.614 AC: 257528 AN: 419710

Other (OTH) AF: 0.624 AC: 20295 AN: 32532

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

African (AFR) AF: 0.893 AC: 37101 AN: 41548

American (AMR) AF: 0.632 AC: 9657 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1892 AN: 3472

East Asian (EAS) AF: 0.577 AC: 2980 AN: 5168

South Asian (SAS) AF: 0.748 AC: 3613 AN: 4830

European-Finnish (FIN) AF: 0.644 AC: 6821 AN: 10592

Middle Eastern (MID) AF: 0.658 AC: 192 AN: 292

European-Non Finnish (NFE) AF: 0.610 AC: 41443 AN: 67980

Other (OTH) AF: 0.651 AC: 1377 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.80
PhyloP100		0.84
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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