Variant 12-52007053-A-G 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.34A>G(p.Lys12Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000307 in 1,303,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000031 ( 0 hom. )

Consequence

TAMALIN
NM_181711.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.961

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:

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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=0.20268342).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAMALIN	NM_181711.4 linkuse as main transcript	c.34A>G	p.Lys12Glu	missense_variant	1/8	ENST00000293662.9	NP_859062.1	Q7Z6J2-1
TAMALIN	XM_047428439.1 linkuse as main transcript	c.-307A>G		5_prime_UTR_variant	1/7		XP_047284395.1
TAMALIN-AS1	NR_146770.1 linkuse as main transcript	n.603T>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.34A>G	p.Lys12Glu	missense_variant	1/8	1	NM_181711.4	ENSP00000293662.4		Q7Z6J2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000307

AC:

AN:

1303308

Hom.:

Cov.:

AF XY:

0.00000312

AC XY:

AN XY:

641754

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:

0.00000383

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

Oct 09, 2024

The c.34A>G (p.K12E) 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 34, causing the lysine (K) at amino acid position 12 to be replaced by a glutamic acid (E). 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

0.27

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Benign

-0.13

Eigen_PC

Benign

0.018

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.51

M_CAP

Pathogenic

0.65

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.15

REVEL

Benign

0.042

Sift

Uncertain

0.012

Sift4G

Benign

0.64

Polyphen

0.28

Vest4

0.18

MutPred

0.26

Loss of ubiquitination at K12 (P = 0.0087);

MVP

0.63

MPC

1.6

ClinPred

0.83

GERP RS

5.2

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

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