6-105176540-T-G

Variant names:

• chr6-105176540-T-G
• rs1190270
• NM_022361.5:c.-252+3293A>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.-252+3293A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 151,936 control chromosomes in the GnomAD database, including 52,957 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 0.82 (52957 hom., cov: 32)
• Consequence: POPDC3 NM_022361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.939
• Publications: 1 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POPDC3	NM_022361.5	c.-252+3293A>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.-252+3293A>C		intron_variant	Intron 1 of 3	1	NM_022361.5	ENSP00000254765.3

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124483 AN: 151818 Hom.: 52928 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.909

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.879

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.853

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

GnomAD4 genome AF: 0.820 AC: 124552 AN: 151936 Hom.: 52957 Cov.: 32 AF XY: 0.823 AC XY: 61100 AN XY: 74264

African (AFR) AF: 0.562 AC: 23254 AN: 41394

American (AMR) AF: 0.899 AC: 13738 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 3172 AN: 3466

East Asian (EAS) AF: 0.903 AC: 4659 AN: 5158

South Asian (SAS) AF: 0.909 AC: 4374 AN: 4810

European-Finnish (FIN) AF: 0.926 AC: 9781 AN: 10568

Middle Eastern (MID) AF: 0.887 AC: 259 AN: 292

European-Non Finnish (NFE) AF: 0.922 AC: 62630 AN: 67948

Other (OTH) AF: 0.854 AC: 1806 AN: 2114

Alfa AF: 0.902 Hom.: 86666

Bravo AF: 0.808

Asia WGS AF: 0.887 AC: 3087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		0.94
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: rs1190270; hg19: chr6-105624415;