rs9913373

Positions:

• chr17-6470241-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_031220.4(PITPNM3):​c.1773+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 1,586,876 control chromosomes in the GnomAD database, including 1,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (277 hom., cov: 33)
  • Exomes 𝑓: 0.031 (1379 hom.)
• Consequence: PITPNM3 NM_031220.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.05

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-6470241-G-A is Benign according to our data. Variant chr17-6470241-G-A is described in ClinVar as [Benign]. Clinvar id is 261942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITPNM3	NM_031220.4	c.1773+19C>T		intron_variant		ENST00000262483.13	NP_112497.2
PITPNM3	NM_001165966.2	c.1665+19C>T		intron_variant			NP_001159438.1
PITPNM3	XM_011524015.4	c.1773+19C>T		intron_variant			XP_011522317.1
PITPNM3	XM_011524016.4	c.1773+19C>T		intron_variant			XP_011522318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITPNM3	ENST00000262483.13	c.1773+19C>T		intron_variant		1	NM_031220.4	ENSP00000262483.8
PITPNM3	ENST00000572795.1	n.4279+19C>T		intron_variant		1
PITPNM3	ENST00000576664.5	n.522+19C>T		intron_variant		1
PITPNM3	ENST00000421306.7	c.1665+19C>T		intron_variant		2		ENSP00000407882.3

Frequencies

GnomAD3 genomes AF: 0.0485 AC: 7379 AN: 152200 Hom.: 274 Cov.: 33

Gnomad AFR AF: 0.0885

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0841

Gnomad ASJ AF: 0.0276

Gnomad EAS AF: 0.0248

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.00508

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0210

Gnomad OTH AF: 0.0497

GnomAD3 exomes AF: 0.0507 AC: 10381 AN: 204588 Hom.: 504 AF XY: 0.0512 AC XY: 5633 AN XY: 110064

Gnomad AFR exome AF: 0.0905

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.0255

Gnomad EAS exome AF: 0.0278

Gnomad SAS exome AF: 0.114

Gnomad FIN exome AF: 0.00784

Gnomad NFE exome AF: 0.0213

Gnomad OTH exome AF: 0.0500

GnomAD4 exome AF: 0.0310 AC: 44430 AN: 1434558 Hom.: 1379 Cov.: 31 AF XY: 0.0329 AC XY: 23369 AN XY: 710978

Gnomad4 AFR exome AF: 0.0952

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.0254

Gnomad4 EAS exome AF: 0.0188

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.00830

Gnomad4 NFE exome AF: 0.0209

Gnomad4 OTH exome AF: 0.0417

GnomAD4 genome AF: 0.0486 AC: 7407 AN: 152318 Hom.: 277 Cov.: 33 AF XY: 0.0490 AC XY: 3650 AN XY: 74482

Gnomad4 AFR AF: 0.0888

Gnomad4 AMR AF: 0.0842

Gnomad4 ASJ AF: 0.0276

Gnomad4 EAS AF: 0.0247

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.00508

Gnomad4 NFE AF: 0.0210

Gnomad4 OTH AF: 0.0506

Alfa AF: 0.0337 Hom.: 30

Bravo AF: 0.0561

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 27, 2019	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 26, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.43

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: rs9913373; hg19: chr17-6373561;