17-6451881-C-CAA

Variant names:

• chr17-6451881-C-CAA
• rs200905881
• NM_031220.4:c.*3456_*3457insTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_031220.4(PITPNM3):​c.*3456_*3457insTT 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 0.15 (667 hom., cov: 20)
  • 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: 0.145
• 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: G2P, Labcorp Genetics (formerly Invitae)
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 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.*3456_*3457insTT		3_prime_UTR	Exon 20 of 20	NP_112497.2	Q9BZ71-1
	PITPNM3	NM_001165966.2		c.*3456_*3457insTT		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.*3456_*3457insTT		3_prime_UTR	Exon 20 of 20	ENSP00000262483.8	Q9BZ71-1
	PITPNM3	ENST00000421306.7	TSL:2	c.*3456_*3457insTT		3_prime_UTR	Exon 19 of 19	ENSP00000407882.3	Q9BZ71-3

Frequencies

GnomAD3 genomes AF: 0.147 AC: 5448 AN: 37068 Hom.: 660 Cov.: 20

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0801

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.0662

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.0992

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 28 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 16

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

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: 24

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.147 AC: 5468 AN: 37092 Hom.: 667 Cov.: 20 AF XY: 0.151 AC XY: 2766 AN XY: 18266

African (AFR) AF: 0.196 AC: 1887 AN: 9628

American (AMR) AF: 0.0800 AC: 267 AN: 3336

Ashkenazi Jewish (ASJ) AF: 0.0746 AC: 77 AN: 1032

East Asian (EAS) AF: 0.167 AC: 269 AN: 1606

South Asian (SAS) AF: 0.262 AC: 247 AN: 942

European-Finnish (FIN) AF: 0.143 AC: 437 AN: 3056

Middle Eastern (MID) AF: 0.0714 AC: 9 AN: 126

European-Non Finnish (NFE) AF: 0.132 AC: 2201 AN: 16728

Other (OTH) AF: 0.127 AC: 62 AN: 490

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200905881; hg19: chr17-6355201;