chr17-6451873-A-AC

Position:

• chr17-6451873-A-AC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_031220.4(PITPNM3):​c.*3464_*3465insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (236 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PITPNM3 NM_031220.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.916

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0322 (1408/43710) while in subpopulation AMR AF= 0.0402 (144/3582). AF 95% confidence interval is 0.0359. There are 236 homozygotes in gnomad4. There are 649 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 1408 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITPNM3	NM_031220.4	c.*3464_*3465insG		3_prime_UTR_variant	20/20	ENST00000262483.13	NP_112497.2
PITPNM3	NM_001165966.2	c.*3464_*3465insG		3_prime_UTR_variant	19/19		NP_001159438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITPNM3	ENST00000262483.13	c.*3464_*3465insG		3_prime_UTR_variant	20/20	1	NM_031220.4	ENSP00000262483	P1
PITPNM3	ENST00000421306.7	c.*3464_*3465insG		3_prime_UTR_variant	19/19	2		ENSP00000407882

Frequencies

GnomAD3 genomes AF: 0.0322 AC: 1407 AN: 43696 Hom.: 236 Cov.: 0

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.0126

Gnomad AMR AF: 0.0402

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.0389

Gnomad SAS AF: 0.0274

Gnomad FIN AF: 0.0245

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0381

Gnomad OTH AF: 0.0234

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0322 AC: 1408 AN: 43710 Hom.: 236 Cov.: 0 AF XY: 0.0322 AC XY: 649 AN XY: 20184

Gnomad4 AFR AF: 0.0209

Gnomad4 AMR AF: 0.0402

Gnomad4 ASJ AF: 0.0360

Gnomad4 EAS AF: 0.0390

Gnomad4 SAS AF: 0.0277

Gnomad4 FIN AF: 0.0245

Gnomad4 NFE AF: 0.0381

Gnomad4 OTH AF: 0.0231

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Cone-Rod Dystrophy, Dominant Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs750929247; hg19: chr17-6355193;