3-33865759-A-T

Position:

• chr3-33865759-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_013374.6(PDCD6IP):​c.2432+329A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 152,284 control chromosomes in the GnomAD database, including 100 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 0.038 (100 hom., cov: 32)
• Consequence: PDCD6IP NM_013374.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101

Genes affected

PDCD6IP (HGNC:8766): (programmed cell death 6 interacting protein) This gene encodes a protein that functions within the ESCRT pathway in the abscission stage of cytokinesis, in intralumenal endosomal vesicle formation, and in enveloped virus budding. Studies using mouse cells have shown that overexpression of this protein can block apoptosis. In addition, the product of this gene binds to the product of the PDCD6 gene, a protein required for apoptosis, in a calcium-dependent manner. This gene product also binds to endophilins, proteins that regulate membrane shape during endocytosis. Overexpression of this gene product and endophilins results in cytoplasmic vacuolization, which may be partly responsible for the protection against cell death. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. Related pseudogenes have been identified on chromosome 15. [provided by RefSeq, Jan 2012]

PDCD6IP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0381 (5807/152284) while in subpopulation AFR AF= 0.0485 (2017/41558). AF 95% confidence interval is 0.0468. There are 100 homozygotes in gnomad4. There are 2854 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 100 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDCD6IP	NM_013374.6	c.2432+329A>T		intron_variant		ENST00000307296.8	NP_037506.2
PDCD6IP	NM_001162429.3	c.2447+329A>T		intron_variant			NP_001155901.1
PDCD6IP	XM_011533252.2	c.1877+329A>T		intron_variant			XP_011531554.1
PDCD6IP	XM_047447042.1	c.1877+329A>T		intron_variant			XP_047302998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDCD6IP	ENST00000307296.8	c.2432+329A>T		intron_variant		1	NM_013374.6	ENSP00000307387.3
PDCD6IP	ENST00000457054.6	c.2447+329A>T		intron_variant		1		ENSP00000411825.2
PDCD6IP	ENST00000473593.1	n.422+329A>T		intron_variant		2
PDCD6IP	ENST00000648706.1	n.*1662+329A>T		intron_variant				ENSP00000497537.1

Frequencies

GnomAD3 genomes AF: 0.0382 AC: 5806 AN: 152166 Hom.: 100 Cov.: 32

Gnomad AFR AF: 0.0486

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.0177

Gnomad SAS AF: 0.0280

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0344

Gnomad OTH AF: 0.0321

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

GnomAD4 genome AF: 0.0381 AC: 5807 AN: 152284 Hom.: 100 Cov.: 32 AF XY: 0.0383 AC XY: 2854 AN XY: 74462

Gnomad4 AFR AF: 0.0485

Gnomad4 AMR AF: 0.0305

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.0175

Gnomad4 SAS AF: 0.0276

Gnomad4 FIN AF: 0.0524

Gnomad4 NFE AF: 0.0344

Gnomad4 OTH AF: 0.0318

Alfa AF: 0.0102 Hom.: 2

Bravo AF: 0.0366

Asia WGS AF: 0.0320 AC: 110 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.77

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: rs9858195; hg19: chr3-33907251;