Variant chr12-52014990-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181711.4(TAMALIN):c.979G>A(p.Ala327Thr) 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: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TAMALIN
NM_181711.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.64

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038078368).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TAMALIN	NM_181711.4 linkuse as main transcript	c.979G>A	p.Ala327Thr	missense_variant	8/8	ENST00000293662.9
TAMALIN	NM_001271856.2 linkuse as main transcript	c.550G>A	p.Ala184Thr	missense_variant	7/7
TAMALIN	XM_005268691.4 linkuse as main transcript	c.589G>A	p.Ala197Thr	missense_variant	8/8
TAMALIN	XM_047428439.1 linkuse as main transcript	c.589G>A	p.Ala197Thr	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAMALIN	ENST00000293662.9 linkuse as main transcript	c.979G>A	p.Ala327Thr	missense_variant	8/8	1	NM_181711.4	P1	Q7Z6J2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

839130

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

389608

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

Sep 13, 2023

The c.979G>A (p.A327T) alteration is located in exon 8 (coding exon 8) of the GRASP gene. This alteration results from a G to A substitution at nucleotide position 979, causing the alanine (A) at amino acid position 327 to be replaced by a threonine (T). 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

0.082

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.42

DANN

Benign

0.89

DEOGEN2

Benign

0.13

T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.34

T;T;T

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.038

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.38

N;N;N

REVEL

Benign

0.035

Sift

Benign

0.74

T;T;T

Sift4G

Benign

0.86

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.027

MutPred

0.24

Gain of phosphorylation at A327 (P = 0.005);.;.;

MVP

0.49

MPC

1.4

ClinPred

0.028

GERP RS

-1.4

Varity_R

0.043

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

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