chr17-6451884-CCG-C

Position:

• chr17-6451884-CCG-C

Variant summary

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

The NM_031220.4(PITPNM3):​c.*3452_*3453del 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 0.071 (798 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 (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITPNM3	NM_031220.4	c.*3452_*3453del		3_prime_UTR_variant	20/20	ENST00000262483.13	NP_112497.2
PITPNM3	NM_001165966.2	c.*3452_*3453del		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.*3452_*3453del		3_prime_UTR_variant	20/20	1	NM_031220.4	ENSP00000262483	P1
PITPNM3	ENST00000421306.7	c.*3452_*3453del		3_prime_UTR_variant	19/19	2		ENSP00000407882

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 5606 AN: 78432 Hom.: 796 Cov.: 0

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0738

Gnomad AMR AF: 0.0677

Gnomad ASJ AF: 0.0891

Gnomad EAS AF: 0.00320

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0178

Gnomad MID AF: 0.106

Gnomad NFE AF: 0.0503

Gnomad OTH AF: 0.0867

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 10 Hom.: 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: 0.0715 AC: 5608 AN: 78484 Hom.: 798 Cov.: 0 AF XY: 0.0671 AC XY: 2570 AN XY: 38278

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0675

Gnomad4 ASJ AF: 0.0891

Gnomad4 EAS AF: 0.00321

Gnomad4 SAS AF: 0.0226

Gnomad4 FIN AF: 0.0178

Gnomad4 NFE AF: 0.0504

Gnomad4 OTH AF: 0.0825

Alfa AF: 0.0416 Hom.: 0

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: rs796279837; hg19: chr17-6355204;