Variant 12-52014975-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181711.4(TAMALIN):c.964C>T(p.Pro322Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000725 in 827,900 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

TAMALIN
NM_181711.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0800

Variant links:

Genes affected

TAMALIN (HGNC:18707): (trafficking regulator and scaffold protein tamalin) This gene encodes a protein that functions as a molecular scaffold, linking receptors, including group 1 metabotropic glutamate receptors, to neuronal proteins. The encoded protein contains conserved domains, including a leucine zipper sequence, PDZ domain and a C-terminal PDZ-binding motif. Alternately spliced transcript variants have been observed for this gene.[provided by RefSeq, Dec 2012]

TAMALIN links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15772834).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TAMALIN	NM_181711.4 linkuse as main transcript	c.964C>T	p.Pro322Ser	missense_variant	8/8	ENST00000293662.9
TAMALIN	NM_001271856.2 linkuse as main transcript	c.535C>T	p.Pro179Ser	missense_variant	7/7
TAMALIN	XM_005268691.4 linkuse as main transcript	c.574C>T	p.Pro192Ser	missense_variant	8/8
TAMALIN	XM_047428439.1 linkuse as main transcript	c.574C>T	p.Pro192Ser	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAMALIN	ENST00000293662.9 linkuse as main transcript	c.964C>T	p.Pro322Ser	missense_variant	8/8	1	NM_181711.4	P1	Q7Z6J2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000725

AC:

AN:

827900

Hom.:

Cov.:

AF XY:

0.0000130

AC XY:

AN XY:

383528

show subpopulations

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:

0.00000795

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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 19, 2022

The c.964C>T (p.P322S) alteration is located in exon 8 (coding exon 8) of the GRASP gene. This alteration results from a C to T substitution at nucleotide position 964, causing the proline (P) at amino acid position 322 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

0.076

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

1.8

DANN

Benign

0.91

DEOGEN2

Benign

0.072

T;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.45

T;T;T

M_CAP

Pathogenic

0.75

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

1.5

N;N;N

REVEL

Benign

0.033

Sift

Benign

0.84

T;T;T

Sift4G

Benign

0.81

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.067

MutPred

0.25

Gain of phosphorylation at P322 (P = 0.0073);.;.;

MVP

0.55

MPC

1.5

ClinPred

0.045

GERP RS

0.96

Varity_R

0.033

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over