Variant 12-52009214-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_181711.4(TAMALIN):c.271C>T(p.Leu91Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,614,072 control chromosomes in the GnomAD database, including 188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0092 ( 11 hom., cov: 32)

Exomes 𝑓: 0.013 ( 177 hom. )

Consequence

TAMALIN
NM_181711.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.16

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005406946).

BP6

Variant 12-52009214-C-T is Benign according to our data. Variant chr12-52009214-C-T is described in ClinVar as [Benign]. Clinvar id is 783034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0135 (19683/1461714) while in subpopulation NFE AF= 0.0154 (17178/1111930). AF 95% confidence interval is 0.0153. There are 177 homozygotes in gnomad4_exome. There are 9630 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TAMALIN	NM_181711.4 linkuse as main transcript	c.271C>T	p.Leu91Phe	missense_variant	2/8	ENST00000293662.9	NP_859062.1
TAMALIN	XM_005268691.4 linkuse as main transcript	c.-120C>T		5_prime_UTR_variant	2/8		XP_005268748.1
TAMALIN	XM_047428439.1 linkuse as main transcript	c.-94-1667C>T		intron_variant			XP_047284395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAMALIN	ENST00000293662.9 linkuse as main transcript	c.271C>T	p.Leu91Phe	missense_variant	2/8	1	NM_181711.4	ENSP00000293662	P1	Q7Z6J2-1
TAMALIN	ENST00000552963.5 linkuse as main transcript	n.27C>T		non_coding_transcript_exon_variant	1/7	1

Frequencies

GnomAD3 genomes

AF:

0.00920

AC:

1401

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00229

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.0109

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.0139

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0144

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00927

AC:

2330

AN:

251334

Hom.:

AF XY:

0.00942

AC XY:

1280

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00585

Gnomad FIN exome

AF:

0.0137

Gnomad NFE exome

AF:

0.0137

Gnomad OTH exome

AF:

0.00831

GnomAD4 exome

AF:

0.0135

AC:

19683

AN:

1461714

Hom.:

177

Cov.:

AF XY:

0.0132

AC XY:

9630

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.00212

Gnomad4 AMR exome

AF:

0.00286

Gnomad4 ASJ exome

AF:

0.0119

Gnomad4 EAS exome

AF:

0.000907

Gnomad4 SAS exome

AF:

0.00607

Gnomad4 FIN exome

AF:

0.0136

Gnomad4 NFE exome

AF:

0.0154

Gnomad4 OTH exome

AF:

0.0116

GnomAD4 genome

AF:

0.00920

AC:

1401

AN:

152358

Hom.:

Cov.:

AF XY:

0.00903

AC XY:

673

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.00228

Gnomad4 AMR

AF:

0.00588

Gnomad4 ASJ

AF:

0.0109

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00455

Gnomad4 FIN

AF:

0.0139

Gnomad4 NFE

AF:

0.0144

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.00779

TwinsUK

AF:

0.0146

AC:

ALSPAC

AF:

0.0153

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.0109

AC:

ExAC

AF:

0.00881

AC:

1069

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0127

EpiControl

AF:

0.0108

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0054

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

0.87

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.2

REVEL

Benign

0.038

Sift

Benign

0.077

Sift4G

Benign

0.085

Polyphen

0.0010

Vest4

0.25

MVP

0.16

MPC

0.95

ClinPred

0.015

GERP RS

3.2

Varity_R

0.073

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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