17-6451884-C-G

Position:

• chr17-6451884-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_031220.4(PITPNM3):​c.*3454G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.00085 (11 hom., cov: 20)
• Consequence: PITPNM3 NM_031220.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-6451884-C-G is Benign according to our data. Variant chr17-6451884-C-G is described in ClinVar as [Benign]. Clinvar id is 2647309.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 67 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITPNM3	NM_031220.4	c.*3454G>C		3_prime_UTR_variant	20/20	ENST00000262483.13	NP_112497.2
PITPNM3	NM_001165966.2	c.*3454G>C		3_prime_UTR_variant	19/19		NP_001159438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITPNM3	ENST00000262483.13	c.*3454G>C		3_prime_UTR_variant	20/20	1	NM_031220.4	ENSP00000262483	P1
PITPNM3	ENST00000421306.7	c.*3454G>C		3_prime_UTR_variant	19/19	2		ENSP00000407882

Frequencies

GnomAD3 genomes AF: 0.000853 AC: 67 AN: 78564 Hom.: 11 Cov.: 20

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00259

Gnomad ASJ AF: 0.00208

Gnomad EAS AF: 0.000267

Gnomad SAS AF: 0.00141

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000415

Gnomad OTH AF: 0.00612

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.000852 AC: 67 AN: 78618 Hom.: 11 Cov.: 20 AF XY: 0.000939 AC XY: 36 AN XY: 38346

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.00259

Gnomad4 ASJ AF: 0.00208

Gnomad4 EAS AF: 0.000268

Gnomad4 SAS AF: 0.00141

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000416

Gnomad4 OTH AF: 0.00596

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

PITPNM3: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs879056505; hg19: chr17-6355204;