17-6451884-C-CT

Position:

• chr17-6451884-C-CT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_031220.4(PITPNM3):​c.*3453_*3454insA 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 0.36 (7115 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: 0.00

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITPNM3	NM_031220.4	c.*3453_*3454insA		3_prime_UTR_variant	20/20	ENST00000262483.13	NP_112497.2
PITPNM3	NM_001165966.2	c.*3453_*3454insA		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.*3453_*3454insA		3_prime_UTR_variant	20/20	1	NM_031220.4	ENSP00000262483	P1
PITPNM3	ENST00000421306.7	c.*3453_*3454insA		3_prime_UTR_variant	19/19	2		ENSP00000407882

Frequencies

GnomAD3 genomes AF: 0.355 AC: 27898 AN: 78486 Hom.: 7113 Cov.: 0

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.335

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.355 AC: 27908 AN: 78540 Hom.: 7115 Cov.: 0 AF XY: 0.364 AC XY: 13933 AN XY: 38312

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.333

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: rs879195140; hg19: chr17-6355204; COSMIC: COSV51471032; COSMIC: COSV51471032;