NM_002809.4:c.*41T>C

Variant names:

• chr17-39997622-T-C
• rs7021
• NM_002809.4:c.*41T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002809.4(PSMD3):​c.*41T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000758 in 1,318,948 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: PSMD3 NM_002809.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 0 publications found

Genes affected

PSMD3 (HGNC:9560): (proteasome 26S subunit, non-ATPase 3) 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. This gene encodes a member of the proteasome subunit S3 family that functions as one of the non-ATPase subunits of the 19S regulator lid. Single nucleotide polymorphisms in this gene are associated with neutrophil count. [provided by RefSeq, Jul 2012]

ENSG00000265799 (HGNC:58140):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD3	NM_002809.4	c.*41T>C		3_prime_UTR_variant	Exon 12 of 12	ENST00000264639.9	NP_002800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD3	ENST00000264639.9	c.*41T>C		3_prime_UTR_variant	Exon 12 of 12	1	NM_002809.4	ENSP00000264639.4
PSMD3	ENST00000540504.2	c.295-172T>C		intron_variant	Intron 3 of 3	3		ENSP00000444980.2
ENSG00000265799	ENST00000801108.1	n.538-8727A>G		intron_variant	Intron 2 of 3
PSMD3	ENST00000415039.7	n.*1213T>C		downstream_gene_variant		2		ENSP00000407410.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.58e-7 AC: 1 AN: 1318948 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 661236

⚠️ 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: 31036

American (AMR) AF: 0.00 AC: 0 AN: 43768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25102

East Asian (EAS) AF: 0.00 AC: 0 AN: 38676

South Asian (SAS) AF: 0.00 AC: 0 AN: 83378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5030

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 985480

Other (OTH) AF: 0.00 AC: 0 AN: 55396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.64
PhyloP100		1.5

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: rs7021; hg19: chr17-38153875;