rs137928260

Variant names:

• chr22-36815119-C-G
• rs137928260
• NM_001315532.2:c.178G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-36815119-C-G
• chr22-36815119-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001315532.2(PVALB):​c.178G>C​(p.Glu60Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E60K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PVALB NM_001315532.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.56

Genes affected

PVALB (HGNC:9704): (parvalbumin) The protein encoded by this gene is a high affinity calcium ion-binding protein that is structurally and functionally similar to calmodulin and troponin C. The encoded protein is thought to be involved in muscle relaxation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.869

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVALB	NM_001315532.2	c.178G>C	p.Glu60Gln	missense_variant	Exon 2 of 4	ENST00000417718.7	NP_001302461.1
PVALB	NM_002854.3	c.178G>C	p.Glu60Gln	missense_variant	Exon 3 of 5		NP_002845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVALB	ENST00000417718.7	c.178G>C	p.Glu60Gln	missense_variant	Exon 2 of 4	1	NM_001315532.2	ENSP00000400247.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251284 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135828

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.70	D;D;T;D
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Pathogenic	0.29	D
MetaRNN	Pathogenic	0.87	D;D;D;D
MetaSVM	Uncertain	0.49	D
MutationAssessor	Pathogenic	3.8	H;H;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.9	D;D;D;D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;.
Polyphen		1.0	D;D;.;.
Vest4		0.84
MutPred		0.66		Loss of ubiquitination at K55 (P = 0.1055);Loss of ubiquitination at K55 (P = 0.1055);.;Loss of ubiquitination at K55 (P = 0.1055);
MVP		0.66
MPC		0.93
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.75
gMVP		0.79

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: rs137928260; hg19: chr22-37211163; COSMIC: COSV53413338; COSMIC: COSV53413338;