rs11962089

Variant names:

• chr6-105164345-A-G
• rs11962089
• NM_022361.5:c.-251-2185T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022361.5(POPDC3):​c.-251-2185T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,192 control chromosomes in the GnomAD database, including 2,783 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2783 hom., cov: 32)
• Consequence: POPDC3 NM_022361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475
• Publications: 18 publications found

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:21223): (BVES antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POPDC3	NM_022361.5	c.-251-2185T>C		intron_variant	Intron 1 of 3	ENST00000254765.4	NP_071756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POPDC3	ENST00000254765.4	c.-251-2185T>C		intron_variant	Intron 1 of 3	1	NM_022361.5	ENSP00000254765.3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24541 AN: 152074 Hom.: 2763 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0733

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.162 AC: 24608 AN: 152192 Hom.: 2783 Cov.: 32 AF XY: 0.159 AC XY: 11842 AN XY: 74426

African (AFR) AF: 0.326 AC: 13532 AN: 41478

American (AMR) AF: 0.109 AC: 1665 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3472

East Asian (EAS) AF: 0.0301 AC: 156 AN: 5190

South Asian (SAS) AF: 0.102 AC: 492 AN: 4826

European-Finnish (FIN) AF: 0.0733 AC: 778 AN: 10612

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.107 AC: 7250 AN: 68002

Other (OTH) AF: 0.142 AC: 300 AN: 2114

Alfa AF: 0.121 Hom.: 5906

Bravo AF: 0.171

Asia WGS AF: 0.0780 AC: 272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.3
DANN	Benign	0.71
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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: rs11962089; hg19: chr6-105612220;