rs40610

Variant names:

• chr3-64023832-T-A
• rs40610
• ENST00000394431.6:c.4A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-64023832-T-A
• chr3-64023832-T-C
• chr3-64023832-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000394431.6(PSMD6):​c.4A>T​(p.Asn2Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000759 in 1,317,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: PSMD6 ENST00000394431.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• Publications: 17 publications found

Genes affected

PSMD6 (HGNC:9564): (proteasome 26S subunit, non-ATPase 6) This gene encodes a member of the protease subunit S10 family. The encoded protein is a subunit of the 26S proteasome which colocalizes with DNA damage foci and is involved in the ATP-dependent degradation of ubiquinated proteins. Alternative splicing results in multiple transcript variants [provided by RefSeq, Nov 2012]

LOC105377121 (HGNC:):

ACMG classification

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=0.110199094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD6	NM_001271780.2	c.4A>T	p.Asn2Tyr	missense_variant	Exon 1 of 8		NP_001258709.1
LOC105377121	XR_940906.3	n.-243T>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD6	ENST00000394431.6	c.4A>T	p.Asn2Tyr	missense_variant	Exon 1 of 8	1		ENSP00000377952.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.59e-7 AC: 1 AN: 1317314 Hom.: 0 Cov.: 31 AF XY: 0.00000153 AC XY: 1 AN XY: 652748

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30036

American (AMR) AF: 0.00 AC: 0 AN: 35462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24782

East Asian (EAS) AF: 0.00 AC: 0 AN: 35292

South Asian (SAS) AF: 0.00 AC: 0 AN: 77336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5568

European-Non Finnish (NFE) AF: 9.81e-7 AC: 1 AN: 1019288

Other (OTH) AF: 0.00 AC: 0 AN: 55712

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	1.9
DANN	Benign	0.62
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.16
PROVEAN	Benign	0.050	N
REVEL	Benign	0.095
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.13
MutPred		0.18		Loss of relative solvent accessibility (P = 0.0981);
MVP		0.043
ClinPred		0.52	D
GERP RS		1.2
PromoterAI		-0.0012	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs40610; hg19: chr3-64009508;