NM_002791.3:c.172-10T>G

Variant names:

• chr14-35308904-T-G
• rs186794633
• NM_002791.3:c.172-10T>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS2

The NM_002791.3(PSMA6):​c.172-10T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000458 in 1,572,524 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (1 hom.)
• Consequence: PSMA6 NM_002791.3 intron
• Scores: Splicing: ADA: 0.6532
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.96
• Publications: 0 publications found

Genes affected

PSMA6 (HGNC:9535): (proteasome 20S subunit alpha 6) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure 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. 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 a member of the peptidase T1A family, that is a 20S core alpha subunit. Multiple transcript variants encoding several different isoforms have been found for this gene. A pseudogene has been identified on the Y chromosome. [provided by RefSeq, Aug 2013]

ENSG00000258790 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 14-35308904-T-G is Benign according to our data. Variant chr14-35308904-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3050747.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 405 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002791.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA6	NM_002791.3	MANE Select	c.172-10T>G		intron	N/A	NP_002782.1	P60900-1
	PSMA6	NM_001282234.1		c.115-10T>G		intron	N/A	NP_001269163.1	P60900-2
	PSMA6	NM_001282232.1		c.-66-10T>G		intron	N/A	NP_001269161.1	P60900-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA6	ENST00000261479.9	TSL:1 MANE Select	c.172-10T>G		intron	N/A	ENSP00000261479.4	P60900-1
	ENSG00000258790	ENST00000557565.1	TSL:2	n.*987-10T>G		intron	N/A	ENSP00000454657.1
	PSMA6	ENST00000553809.5	TSL:3	c.172-10T>G		intron	N/A	ENSP00000452603.1	G3V5Z7

Frequencies

GnomAD3 genomes AF: 0.00265 AC: 404 AN: 152222 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00916

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000703 AC: 166 AN: 235992 AF XY: 0.000570

Gnomad AFR exome AF: 0.00984

Gnomad AMR exome AF: 0.000408

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000222 AC: 315 AN: 1420184 Hom.: 1 Cov.: 27 AF XY: 0.000198 AC XY: 140 AN XY: 707996

African (AFR) AF: 0.00840 AC: 268 AN: 31916

American (AMR) AF: 0.000431 AC: 17 AN: 39450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25488

East Asian (EAS) AF: 0.00 AC: 0 AN: 39412

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.00000277 AC: 3 AN: 1083980

Other (OTH) AF: 0.000440 AC: 26 AN: 59074

GnomAD4 genome AF: 0.00266 AC: 405 AN: 152340 Hom.: 2 Cov.: 32 AF XY: 0.00248 AC XY: 185 AN XY: 74500

African (AFR) AF: 0.00916 AC: 381 AN: 41588

American (AMR) AF: 0.00131 AC: 20 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00226 Hom.: 0

Bravo AF: 0.00306

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PSMA6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Benign	0.73
PhyloP100		3.0
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.65
dbscSNV1_RF	Benign	0.69
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: rs186794633; hg19: chr14-35778110;