rs773030993

Variant names:

• chr22-36816953-G-T
• rs773030993
• NM_001315532.2:c.53C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001315532.2(PVALB):​c.53C>A​(p.Ala18Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000412 in 1,455,420 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PVALB NM_001315532.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.96
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001315532.2. 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
	PVALB	NM_001315532.2	MANE Select	c.53C>A	p.Ala18Asp	missense	Exon 1 of 4	NP_001302461.1	P20472
	PVALB	NM_002854.3		c.53C>A	p.Ala18Asp	missense	Exon 2 of 5	NP_002845.1	P20472

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVALB	ENST00000417718.7	TSL:1 MANE Select	c.53C>A	p.Ala18Asp	missense	Exon 1 of 4	ENSP00000400247.2	P20472
	PVALB	ENST00000216200.9	TSL:1	c.53C>A	p.Ala18Asp	missense	Exon 2 of 5	ENSP00000216200.5	P20472
	PVALB	ENST00000912200.1		c.53C>A	p.Ala18Asp	missense	Exon 2 of 5	ENSP00000582259.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000820 AC: 2 AN: 243994 AF XY: 0.0000151

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000296

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000901

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1455420 Hom.: 0 Cov.: 31 AF XY: 0.00000691 AC XY: 5 AN XY: 724020

African (AFR) AF: 0.00 AC: 0 AN: 32898

American (AMR) AF: 0.0000225 AC: 1 AN: 44414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26010

East Asian (EAS) AF: 0.00 AC: 0 AN: 39374

South Asian (SAS) AF: 0.00 AC: 0 AN: 85378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4644

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110500

Other (OTH) AF: 0.0000499 AC: 3 AN: 60106

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.45
Sift	Benign	0.15	T
Sift4G	Benign	0.31	T
Polyphen		0.98	D
Vest4		0.68
MutPred		0.34		Loss of catalytic residue at A18 (P = 0.0083)
MVP		0.59
MPC		0.97
ClinPred		0.89	D
GERP RS		4.0
PromoterAI		-0.0050	Neutral
Varity_R		0.62
gMVP		0.93
Mutation Taster		=37/63	disease causing

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: rs773030993; hg19: chr22-37212997;