17-6518129-G-T

Variant names:

• chr17-6518129-G-T
• rs952849
• NM_031220.4:c.226+7227C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

PITPNM3 Gene-Disease associations (from GenCC):

• cone-rod dystrophy 5

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PITPNM3	NM_031220.4	c.226+7227C>A		intron_variant	Intron 3 of 19	ENST00000262483.13	NP_112497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITPNM3	ENST00000262483.13	c.226+7227C>A		intron_variant	Intron 3 of 19	1	NM_031220.4	ENSP00000262483.8
PITPNM3	ENST00000421306.7	c.119-14555C>A		intron_variant	Intron 2 of 18	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

African (AFR) AF: 0.265 AC: 10972 AN: 41456

American (AMR) AF: 0.0385 AC: 589 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0355 AC: 123 AN: 3468

East Asian (EAS) AF: 0.161 AC: 834 AN: 5186

South Asian (SAS) AF: 0.0627 AC: 302 AN: 4820

European-Finnish (FIN) AF: 0.00906 AC: 96 AN: 10594

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0143 AC: 975 AN: 68014

Other (OTH) AF: 0.0701 AC: 148 AN: 2112

Alfa AF: 0.0488 Hom.: 985

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
PhyloP100		-0.55
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: rs952849; hg19: chr17-6421449;