Variant 11-67492275-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004910.3(PITPNM1):c.3493G>T(p.Ala1165Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PITPNM1
NM_004910.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87

Variant links:

Genes affected

PITPNM1 (HGNC:9003): (phosphatidylinositol transfer protein membrane associated 1) PITPNM1 belongs to a family of membrane-associated phosphatidylinositol transfer domain-containing proteins that share homology with the Drosophila retinal degeneration B (rdgB) protein (Ocaka et al., 2005 [PubMed 15627748]).[supplied by OMIM, Mar 2008]

PITPNM1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29657406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PITPNM1	NM_004910.3 linkuse as main transcript	c.3493G>T	p.Ala1165Ser	missense_variant	24/24	ENST00000356404.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITPNM1	ENST00000356404.8 linkuse as main transcript	c.3493G>T	p.Ala1165Ser	missense_variant	24/24	1	NM_004910.3	P5	O00562-1
PITPNM1	ENST00000534749.5 linkuse as main transcript	c.3493G>T	p.Ala1165Ser	missense_variant	23/23	1		P5	O00562-1
PITPNM1	ENST00000436757.6 linkuse as main transcript	c.3490G>T	p.Ala1164Ser	missense_variant	24/24	1		A1	O00562-2
PITPNM1	ENST00000527370.5 linkuse as main transcript	n.3206G>T		non_coding_transcript_exon_variant	13/13	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1430050

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

708154

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 26, 2023

The c.3493G>T (p.A1165S) alteration is located in exon 24 (coding exon 23) of the PITPNM1 gene. This alteration results from a G to T substitution at nucleotide position 3493, causing the alanine (A) at amino acid position 1165 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;.;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.89

M_CAP

Benign

0.037

MetaRNN

Benign

0.30

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.2

L;.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.065

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.51

T;T;T

Polyphen

0.91

P;D;P

Vest4

0.23

MutPred

0.41

Gain of disorder (P = 0.0362);.;Gain of disorder (P = 0.0362);

MVP

0.33

MPC

1.1

ClinPred

0.71

GERP RS

5.0

Varity_R

0.13

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over