chr17-6518129-G-T

Position:

• chr17-6518129-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031220.4(PITPNM3):​c.226+7227C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0923 in 152,148 control chromosomes in the GnomAD database, including 1,551 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 0.092 (1551 hom., cov: 32)
• Consequence: PITPNM3 NM_031220.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550

Genes affected

PITPNM3 (HGNC:21043): (PITPNM family member 3) This gene encodes a member of a family of membrane-associated phosphatidylinositol transfer domain-containing proteins. The calcium-binding protein has phosphatidylinositol (PI) transfer activity and interacts with the protein tyrosine kinase PTK2B (also known as PYK2). The protein is homologous to a Drosophila protein that is implicated in the visual transduction pathway in flies. Mutations in this gene result in autosomal dominant cone dystrophy. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITPNM3	NM_031220.4	c.226+7227C>A		intron_variant		ENST00000262483.13	NP_112497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITPNM3	ENST00000262483.13	c.226+7227C>A		intron_variant		1	NM_031220.4	ENSP00000262483.8
PITPNM3	ENST00000421306.7	c.119-14555C>A		intron_variant		2		ENSP00000407882.3

Frequencies

GnomAD3 genomes AF: 0.0921 AC: 14009 AN: 152030 Hom.: 1546 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0386

Gnomad ASJ AF: 0.0355

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0622

Gnomad FIN AF: 0.00906

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.0713

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

GnomAD4 genome AF: 0.0923 AC: 14050 AN: 152148 Hom.: 1551 Cov.: 32 AF XY: 0.0910 AC XY: 6767 AN XY: 74380

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.0385

Gnomad4 ASJ AF: 0.0355

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.0627

Gnomad4 FIN AF: 0.00906

Gnomad4 NFE AF: 0.0143

Gnomad4 OTH AF: 0.0701

Alfa AF: 0.0103 Hom.: 3

Bravo AF: 0.102

Asia WGS AF: 0.0980 AC: 342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.56

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: rs952849; hg19: chr17-6421449;