rs750929247

Variant names:

• chr17-6451873-ACCC-A
• rs750929247
• NM_031220.4:c.*3462_*3464delGGG

Your query was ambiguous. Multiple possible variants found:

• chr17-6451873-ACCC-A
• chr17-6451873-ACCC-AC
• chr17-6451873-ACCC-ACC
• chr17-6451873-ACCC-ACCCC
• chr17-6451873-ACCC-ACCCCC
• chr17-6451873-ACCC-ACCCCCC
• chr17-6451873-ACCC-ACCCCCCC
• chr17-6451873-ACCC-ACCCCCCCC
• chr17-6451873-ACCC-ACCCCCCCCC
• chr17-6451873-ACCC-ACCCCCCCCCC
• chr17-6451873-ACCC-ACCCCCCCCCCC
• chr17-6451873-ACCC-ACCCCCCCCCCCCC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_031220.4(PITPNM3):​c.*3462_*3464delGGG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PITPNM3 NM_031220.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.695
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.*3462_*3464delGGG		3_prime_UTR	Exon 20 of 20	NP_112497.2	Q9BZ71-1
	PITPNM3	NM_001165966.2		c.*3462_*3464delGGG		3_prime_UTR	Exon 19 of 19	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.*3462_*3464delGGG		3_prime_UTR	Exon 20 of 20	ENSP00000262483.8	Q9BZ71-1
	PITPNM3	ENST00000421306.7	TSL:2	c.*3462_*3464delGGG		3_prime_UTR	Exon 19 of 19	ENSP00000407882.3	Q9BZ71-3

Frequencies

GnomAD3 genomes AF: 0.0000455 AC: 2 AN: 43914 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000276

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000462

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 12 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0000455 AC: 2 AN: 43914 Hom.: 0 Cov.: 0 AF XY: 0.0000986 AC XY: 2 AN XY: 20284

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 11826

American (AMR) AF: 0.000276 AC: 1 AN: 3626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1310

East Asian (EAS) AF: 0.00 AC: 0 AN: 1404

South Asian (SAS) AF: 0.00 AC: 0 AN: 990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 84

European-Non Finnish (NFE) AF: 0.0000462 AC: 1 AN: 21656

Other (OTH) AF: 0.00 AC: 0 AN: 518

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism

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

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

Other links and lift over

dbSNP: rs750929247;

hg19: chr17-6355193;