17-6451881-C-CAA

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITPNM3	NM_031220.4	c.*3456_*3457insTT		3_prime_UTR_variant	Exon 20 of 20	ENST00000262483.13	NP_112497.2
PITPNM3	NM_001165966.2	c.*3456_*3457insTT		3_prime_UTR_variant	Exon 19 of 19		NP_001159438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITPNM3	ENST00000262483	c.*3456_*3457insTT		3_prime_UTR_variant	Exon 20 of 20	1	NM_031220.4	ENSP00000262483.8
PITPNM3	ENST00000421306	c.*3456_*3457insTT		3_prime_UTR_variant	Exon 19 of 19	2		ENSP00000407882.3

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.0800

Gnomad4 ASJ AF: 0.0746

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs200905881; hg19: chr17-6355201;