Genetic Variant TAMALIN:p.Gly362Arg (chr12-52015095-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_181711.4(TAMALIN):c.1084G>C(p.Gly362Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,402,212 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G362S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TAMALIN
NM_181711.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.947

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181711.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAMALIN	NM_181711.4	MANE Select	c.1084G>C	p.Gly362Arg	missense	Exon 8 of 8	NP_859062.1
	TAMALIN	NM_001271856.2		c.655G>C	p.Gly219Arg	missense	Exon 7 of 7	NP_001258785.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TAMALIN	ENST00000293662.9	TSL:1 MANE Select	c.1084G>C	p.Gly362Arg	missense	Exon 8 of 8	ENSP00000293662.4
TAMALIN	ENST00000552049.5	TSL:1	c.655G>C	p.Gly219Arg	missense	Exon 7 of 7	ENSP00000449492.1
TAMALIN	ENST00000552963.5	TSL:1	n.840G>C		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1402212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

695196

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31688

American (AMR)

AF:

0.00

AC:

AN:

37614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24968

East Asian (EAS)

AF:

0.0000271

AC:

AN:

36914

South Asian (SAS)

AF:

0.00

AC:

AN:

81782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34792

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5470

European-Non Finnish (NFE)

AF:

9.17e-7

AC:

AN:

1090504

Other (OTH)

AF:

0.00

AC:

AN:

58480

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.48

Eigen

Benign

0.10

Eigen_PC

Benign

-0.040

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.73

M_CAP

Pathogenic

0.99

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.0

PhyloP100

0.95

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.38

Sift

Uncertain

0.0040

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.18

MutPred

0.51

Gain of MoRF binding (P = 0.0183)

MVP

0.86

MPC

3.0

ClinPred

0.92

GERP RS

3.8

Varity_R

0.11

gMVP

0.47

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over