6-105158695-T-A

Position:

• chr6-105158695-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_022361.5(POPDC3):​c.651A>T​(p.Leu217Phe) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: POPDC3 NM_022361.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -1.76

Genes affected

POPDC3 (HGNC:17649): (popeye domain containing 3) This gene encodes a member of the POP family of proteins containing three putative transmembrane domains. This gene is expressed in cardiac and skeletal muscle and may play an important role in these tissues during development. Alternatively spliced transcript variants have been found. [provided by RefSeq, Nov 2008]

BVES-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.893
• PP5: Variant 6-105158695-T-A is Pathogenic according to our data. Variant chr6-105158695-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 869188.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POPDC3	NM_022361.5	c.651A>T	p.Leu217Phe	missense_variant	4/4	ENST00000254765.4	NP_071756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POPDC3	ENST00000254765.4	c.651A>T	p.Leu217Phe	missense_variant	4/4	1	NM_022361.5	ENSP00000254765.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250528 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135458

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: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Muscular dystrophy, limb-girdle, autosomal recessive 26 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 21, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.84	T;T
M_CAP	Uncertain	0.090	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.7	D;D
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.91
MutPred		0.90		Gain of methylation at K216 (P = 0.0263);.;
MVP		0.12
MPC		0.79
ClinPred		0.99	D
GERP RS		-5.6
Varity_R		0.71
gMVP		0.85

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: rs1054547392; hg19: chr6-105606570;