Variant 12-52007038-A-G 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.19A>G(p.Arg7Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,444,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

TAMALIN
NM_181711.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

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-AS1 (HGNC:):

TAMALIN-AS1 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=0.008861482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAMALIN	NM_181711.4 linkuse as main transcript	c.19A>G	p.Arg7Gly	missense_variant	1/8	ENST00000293662.9	NP_859062.1	Q7Z6J2-1
TAMALIN	XM_047428439.1 linkuse as main transcript	c.-322A>G		5_prime_UTR_variant	1/7		XP_047284395.1
TAMALIN-AS1	NR_146770.1 linkuse as main transcript	n.618T>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAMALIN	ENST00000293662.9 linkuse as main transcript	c.19A>G	p.Arg7Gly	missense_variant	1/8	1	NM_181711.4	ENSP00000293662.4		Q7Z6J2-1

Frequencies

GnomAD3 genomes

AF:

0.000119

AC:

AN:

151844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000549

AC:

AN:

54614

Hom.:

AF XY:

0.0000614

AC XY:

AN XY:

32572

show subpopulations

Gnomad AFR exome

AF:

0.00134

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000996

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000192

AC:

248

AN:

1292392

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

130

AN XY:

635862

show subpopulations

Gnomad4 AFR exome

AF:

0.000156

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:

0.000230

Gnomad4 OTH exome

AF:

0.0000936

GnomAD4 genome

AF:

0.000119

AC:

AN:

151844

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74138

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000132

ExAC

AF:

0.0000532

AC:

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

Jul 30, 2024

The c.19A>G (p.R7G) alteration is located in exon 1 (coding exon 1) of the GRASP gene. This alteration results from a A to G substitution at nucleotide position 19, causing the arginine (R) at amino acid position 7 to be replaced by a glycine (G). 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

Pathogenic

0.62

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.046

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0089

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.8

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.35

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.015

Polyphen

0.0020

Vest4

0.33

MutPred

0.26

Gain of loop (P = 0.0051);

MVP

0.96

MPC

0.73

ClinPred

0.092

GERP RS

3.9

Varity_R

0.17

gMVP

0.32

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