rs75323938

Positions:

• chr17-6464150-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_031220.4(PITPNM3):​c.2156+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,614,096 control chromosomes in the GnomAD database, including 227 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0096 (14 hom., cov: 33)
  • Exomes 𝑓: 0.016 (213 hom.)
• Consequence: PITPNM3 NM_031220.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.505

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-6464150-G-A is Benign according to our data. Variant chr17-6464150-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00958 (1458/152266) while in subpopulation NFE AF= 0.0165 (1120/68010). AF 95% confidence interval is 0.0157. There are 14 homozygotes in gnomad4. There are 634 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1458 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PITPNM3	NM_031220.4	c.2156+20C>T		intron_variant		ENST00000262483.13
PITPNM3	NM_001165966.2	c.2048+20C>T		intron_variant
PITPNM3	XM_011524015.4	c.2156+20C>T		intron_variant
PITPNM3	XM_011524016.4	c.2156+20C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITPNM3	ENST00000262483.13	c.2156+20C>T		intron_variant		1	NM_031220.4	P1
PITPNM3	ENST00000572795.1	n.4662+20C>T		intron_variant, non_coding_transcript_variant		1
PITPNM3	ENST00000576664.5	n.905+20C>T		intron_variant, non_coding_transcript_variant		1
PITPNM3	ENST00000421306.7	c.2048+20C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00958 AC: 1457 AN: 152148 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00753

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0165

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00838 AC: 2096 AN: 250086 Hom.: 14 AF XY: 0.00857 AC XY: 1160 AN XY: 135324

Gnomad AFR exome AF: 0.00209

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00407

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00144

Gnomad FIN exome AF: 0.00851

Gnomad NFE exome AF: 0.0147

Gnomad OTH exome AF: 0.00848

GnomAD4 exome AF: 0.0156 AC: 22802 AN: 1461830 Hom.: 213 Cov.: 33 AF XY: 0.0152 AC XY: 11040 AN XY: 727220

Gnomad4 AFR exome AF: 0.00251

Gnomad4 AMR exome AF: 0.00284

Gnomad4 ASJ exome AF: 0.00497

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00148

Gnomad4 FIN exome AF: 0.00854

Gnomad4 NFE exome AF: 0.0189

Gnomad4 OTH exome AF: 0.0145

GnomAD4 genome AF: 0.00958 AC: 1458 AN: 152266 Hom.: 14 Cov.: 33 AF XY: 0.00852 AC XY: 634 AN XY: 74442

Gnomad4 AFR AF: 0.00344

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00753

Gnomad4 NFE AF: 0.0165

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.0133 Hom.: 2

Bravo AF: 0.00941

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.60

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: rs75323938; hg19: chr17-6367470;