rs11654175

Variant names:

• chr17-6470417-C-T
• rs11654175
• NM_031220.4:c.1625-9G>A

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.1625-9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 1,613,536 control chromosomes in the GnomAD database, including 148,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11240 hom., cov: 33)
  • Exomes 𝑓: 0.43 (137527 hom.)
• Consequence: PITPNM3 NM_031220.4 intron
• Scores: Splicing: ADA: 0.00009036
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.428
• Publications: 10 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: Labcorp Genetics (formerly Invitae), G2P
• 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=-0.83).
• BP6: Variant 17-6470417-C-T is Benign according to our data. Variant chr17-6470417-C-T is described in ClinVar as Benign. ClinVar VariationId is 194273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 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.1625-9G>A		intron	N/A	NP_112497.2	Q9BZ71-1
	PITPNM3	NM_001165966.2		c.1517-9G>A		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.1625-9G>A		intron	N/A	ENSP00000262483.8	Q9BZ71-1
	PITPNM3	ENST00000572795.1	TSL:1	n.4131-9G>A		intron	N/A
	PITPNM3	ENST00000576664.5	TSL:1	n.374-9G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55545 AN: 151942 Hom.: 11240 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.416

GnomAD2 exomes AF: 0.377 AC: 94198 AN: 249992 AF XY: 0.380

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.338

Gnomad ASJ exome AF: 0.470

Gnomad EAS exome AF: 0.193

Gnomad FIN exome AF: 0.424

Gnomad NFE exome AF: 0.460

Gnomad OTH exome AF: 0.425

GnomAD4 exome AF: 0.426 AC: 623070 AN: 1461476 Hom.: 137527 Cov.: 60 AF XY: 0.423 AC XY: 307435 AN XY: 727016

African (AFR) AF: 0.195 AC: 6544 AN: 33478

American (AMR) AF: 0.340 AC: 15212 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 12197 AN: 26130

East Asian (EAS) AF: 0.184 AC: 7306 AN: 39692

South Asian (SAS) AF: 0.251 AC: 21663 AN: 86238

European-Finnish (FIN) AF: 0.421 AC: 22403 AN: 53254

Middle Eastern (MID) AF: 0.478 AC: 2758 AN: 5768

European-Non Finnish (NFE) AF: 0.459 AC: 509819 AN: 1111832

Other (OTH) AF: 0.417 AC: 25168 AN: 60382

GnomAD4 genome AF: 0.365 AC: 55548 AN: 152060 Hom.: 11240 Cov.: 33 AF XY: 0.362 AC XY: 26940 AN XY: 74320

African (AFR) AF: 0.205 AC: 8507 AN: 41520

American (AMR) AF: 0.377 AC: 5757 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1589 AN: 3464

East Asian (EAS) AF: 0.188 AC: 968 AN: 5162

South Asian (SAS) AF: 0.229 AC: 1104 AN: 4826

European-Finnish (FIN) AF: 0.438 AC: 4618 AN: 10550

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31530 AN: 67938

Other (OTH) AF: 0.412 AC: 867 AN: 2106

Alfa AF: 0.427 Hom.: 8060

Bravo AF: 0.358

Asia WGS AF: 0.220 AC: 771 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Cone-rod dystrophy 5 (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.61
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000090
dbscSNV1_RF	Benign	0.0020
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11654175;

hg19: chr17-6373737;

COSMIC: COSV52592826;