rs773030993

Variant names:

• chr22-36816953-G-A
• NM_001315532.2:c.53C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-36816953-G-A
• chr22-36816953-G-C
• chr22-36816953-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001315532.2(PVALB):​c.53C>T​(p.Ala18Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,420 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A18D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PVALB NM_001315532.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.96

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]

ENSG00000234979 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVALB	NM_001315532.2	c.53C>T	p.Ala18Val	missense_variant	Exon 1 of 4	ENST00000417718.7	NP_001302461.1
PVALB	NM_002854.3	c.53C>T	p.Ala18Val	missense_variant	Exon 2 of 5		NP_002845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVALB	ENST00000417718.7	c.53C>T	p.Ala18Val	missense_variant	Exon 1 of 4	1	NM_001315532.2	ENSP00000400247.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455420 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724020

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: 0.0000192

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.56	D;D;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Uncertain	0.25	D
MutationAssessor	Pathogenic	3.4	M;M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.5	N;N;N
REVEL	Uncertain	0.50
Sift	Uncertain	0.020	D;D;D
Sift4G	Benign	0.073	T;T;.
Polyphen		0.98	D;D;.
Vest4		0.51
MutPred		0.36		Loss of disorder (P = 0.0677);Loss of disorder (P = 0.0677);Loss of disorder (P = 0.0677);
MVP		0.55
MPC		0.35
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.58
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-37212997;