rs9913373

Variant names:

• chr17-6470241-G-A
• rs9913373
• NM_031220.4:c.1773+19C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031220.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITPNM3	NM_031220.4	MANE Select	c.1773+19C>T		intron	N/A	NP_112497.2	Q9BZ71-1
	PITPNM3	NM_001165966.2		c.1665+19C>T		intron	N/A	NP_001159438.1	Q9BZ71-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITPNM3	ENST00000262483.13	TSL:1 MANE Select	c.1773+19C>T		intron	N/A	ENSP00000262483.8	Q9BZ71-1
	PITPNM3	ENST00000572795.1	TSL:1	n.4279+19C>T		intron	N/A
	PITPNM3	ENST00000576664.5	TSL:1	n.522+19C>T		intron	N/A

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

GnomAD2 exomes AF: 0.0507 AC: 10381 AN: 204588 AF XY: 0.0512

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 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

African (AFR) AF: 0.0952 AC: 3148 AN: 33058

American (AMR) AF: 0.109 AC: 4334 AN: 39596

Ashkenazi Jewish (ASJ) AF: 0.0254 AC: 651 AN: 25616

East Asian (EAS) AF: 0.0188 AC: 726 AN: 38634

South Asian (SAS) AF: 0.111 AC: 9215 AN: 83144

European-Finnish (FIN) AF: 0.00830 AC: 422 AN: 50836

Middle Eastern (MID) AF: 0.0771 AC: 439 AN: 5694

European-Non Finnish (NFE) AF: 0.0209 AC: 23011 AN: 1098482

Other (OTH) AF: 0.0417 AC: 2484 AN: 59498

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

African (AFR) AF: 0.0888 AC: 3689 AN: 41558

American (AMR) AF: 0.0842 AC: 1288 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0276 AC: 96 AN: 3472

East Asian (EAS) AF: 0.0247 AC: 128 AN: 5182

South Asian (SAS) AF: 0.122 AC: 590 AN: 4822

European-Finnish (FIN) AF: 0.00508 AC: 54 AN: 10628

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0210 AC: 1428 AN: 68030

Other (OTH) AF: 0.0506 AC: 107 AN: 2114

Alfa AF: 0.0351 Hom.: 31

Bravo AF: 0.0561

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.43
PhyloP100		-1.1
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: rs9913373; hg19: chr17-6373561;