Variant 12-52014978-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000293662.9(TAMALIN):c.967G>A(p.Gly323Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000485 in 824,856 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: 0.0000048 ( 0 hom. )

Consequence

TAMALIN
ENST00000293662.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62

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:

TAMALIN (HGNC:):

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=0.1519061).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAMALIN	NM_181711.4 linkuse as main transcript	c.967G>A	p.Gly323Arg	missense_variant	8/8	ENST00000293662.9	NP_859062.1	Q7Z6J2-1
TAMALIN	NM_001271856.2 linkuse as main transcript	c.538G>A	p.Gly180Arg	missense_variant	7/7		NP_001258785.1	Q7Z6J2-2
TAMALIN	XM_005268691.4 linkuse as main transcript	c.577G>A	p.Gly193Arg	missense_variant	8/8		XP_005268748.1
TAMALIN	XM_047428439.1 linkuse as main transcript	c.577G>A	p.Gly193Arg	missense_variant	7/7		XP_047284395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAMALIN	ENST00000293662.9 linkuse as main transcript	c.967G>A	p.Gly323Arg	missense_variant	8/8	1	NM_181711.4	ENSP00000293662.4		Q7Z6J2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000485

AC:

AN:

824856

Hom.:

Cov.:

AF XY:

0.00000523

AC XY:

AN XY:

382354

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:

0.000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000266

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

Nov 18, 2022

The c.967G>A (p.G323R) 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 967, causing the glycine (G) at amino acid position 323 to be replaced by an arginine (R). 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

0.16

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.081

T;.;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.56

T;T;T

M_CAP

Pathogenic

0.83

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

1.1

N;N;N

REVEL

Benign

0.084

Sift

Benign

0.61

T;T;D

Sift4G

Benign

0.078

T;D;T

Polyphen

0.18

B;B;.

Vest4

0.12

MutPred

0.26

Gain of methylation at G323 (P = 0.0055);.;.;

MVP

0.58

MPC

1.7

ClinPred

0.16

GERP RS

2.9

Varity_R

0.034

gMVP

0.29

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