6-3259039-T-C

Position:

• chr6-3259039-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001128591.2(PSMG4):​c.17T>C​(p.Val6Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PSMG4 NM_001128591.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.674

Genes affected

PSMG4 (HGNC:21108): (proteasome assembly chaperone 4) Predicted to be involved in proteasome assembly. Predicted to be part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038975745).
• BP6: Variant 6-3259039-T-C is Benign according to our data. Variant chr6-3259039-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3311050.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMG4	NM_001128591.2	c.17T>C	p.Val6Ala	missense_variant	1/3	ENST00000438998.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMG4	ENST00000438998.7	c.17T>C	p.Val6Ala	missense_variant	1/3	2	NM_001128591.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1098574 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 521254

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.7
DANN	Benign	0.53
DEOGEN2	Benign	0.0021	T;.;.;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.35	T;T;T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.039	T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.4	N;.;N;N;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.94	N;N;N;N;N
REVEL	Benign	0.035
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0	B;.;.;.;.
Vest4		0.053
MutPred		0.34		Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);
MVP		0.014
ClinPred		0.055	T
GERP RS		3.0
Varity_R		0.038
gMVP		0.075

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: rs1757861282; hg19: chr6-3259273;