rs34897053

Variant names:

• chr17-6483627-G-A
• rs34897053
• NM_031220.4:c.477C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-6483627-G-A
• chr17-6483627-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_031220.4(PITPNM3):​c.477C>T​(p.Ser159Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 1,614,062 control chromosomes in the GnomAD database, including 1,644 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S159S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.030 (142 hom., cov: 31)
  • Exomes 𝑓: 0.033 (1502 hom.)
• Consequence: PITPNM3 NM_031220.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -4.51
• Publications: 7 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 17-6483627-G-A is Benign according to our data. Variant chr17-6483627-G-A is described in ClinVar as Benign. ClinVar VariationId is 261948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITPNM3	NM_031220.4	c.477C>T	p.Ser159Ser	synonymous_variant	Exon 6 of 20	ENST00000262483.13	NP_112497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITPNM3	ENST00000262483.13	c.477C>T	p.Ser159Ser	synonymous_variant	Exon 6 of 20	1	NM_031220.4	ENSP00000262483.8
PITPNM3	ENST00000421306.7	c.369C>T	p.Ser123Ser	synonymous_variant	Exon 5 of 19	2		ENSP00000407882.3

Frequencies

GnomAD3 genomes AF: 0.0301 AC: 4583 AN: 152058 Hom.: 140 Cov.: 31

Gnomad AFR AF: 0.00891

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0780

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0240

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0231

Gnomad OTH AF: 0.0413

GnomAD2 exomes AF: 0.0499 AC: 12539 AN: 251264 AF XY: 0.0519

Gnomad AFR exome AF: 0.00837

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.0390

Gnomad EAS exome AF: 0.0669

Gnomad FIN exome AF: 0.0238

Gnomad NFE exome AF: 0.0227

Gnomad OTH exome AF: 0.0491

GnomAD4 exome AF: 0.0330 AC: 48215 AN: 1461886 Hom.: 1502 Cov.: 32 AF XY: 0.0354 AC XY: 25745 AN XY: 727246

African (AFR) AF: 0.00863 AC: 289 AN: 33480

American (AMR) AF: 0.105 AC: 4687 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0388 AC: 1014 AN: 26136

East Asian (EAS) AF: 0.0562 AC: 2232 AN: 39700

South Asian (SAS) AF: 0.118 AC: 10153 AN: 86258

European-Finnish (FIN) AF: 0.0228 AC: 1217 AN: 53420

Middle Eastern (MID) AF: 0.0758 AC: 437 AN: 5768

European-Non Finnish (NFE) AF: 0.0231 AC: 25736 AN: 1112006

Other (OTH) AF: 0.0406 AC: 2450 AN: 60396

GnomAD4 genome AF: 0.0301 AC: 4586 AN: 152176 Hom.: 142 Cov.: 31 AF XY: 0.0325 AC XY: 2415 AN XY: 74416

African (AFR) AF: 0.00888 AC: 369 AN: 41532

American (AMR) AF: 0.0781 AC: 1194 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3468

East Asian (EAS) AF: 0.0614 AC: 316 AN: 5144

South Asian (SAS) AF: 0.131 AC: 631 AN: 4812

European-Finnish (FIN) AF: 0.0240 AC: 254 AN: 10602

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0231 AC: 1568 AN: 68016

Other (OTH) AF: 0.0437 AC: 92 AN: 2104

Alfa AF: 0.0180 Hom.: 18

Bravo AF: 0.0330

Asia WGS AF: 0.110 AC: 382 AN: 3478

EpiCase AF: 0.0244

EpiControl AF: 0.0260

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

May 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cone-rod dystrophy 5 Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.98
DANN	Benign	0.70
PhyloP100		-4.5
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: rs34897053; hg19: chr17-6386947; COSMIC: COSV52598343; COSMIC: COSV52598343;