12-52015095-G-T

Position:

• chr12-52015095-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_181711.4(TAMALIN):​c.1084G>T​(p.Gly362Cys) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.947

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAMALIN	NM_181711.4	c.1084G>T	p.Gly362Cys	missense_variant	8/8	ENST00000293662.9
TAMALIN	NM_001271856.2	c.655G>T	p.Gly219Cys	missense_variant	7/7
TAMALIN	XM_005268691.4	c.694G>T	p.Gly232Cys	missense_variant	8/8
TAMALIN	XM_047428439.1	c.694G>T	p.Gly232Cys	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAMALIN	ENST00000293662.9	c.1084G>T	p.Gly362Cys	missense_variant	8/8	1	NM_181711.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000631 AC: 1 AN: 158510 Hom.: 0 AF XY: 0.0000113 AC XY: 1 AN XY: 88766

Gnomad AFR exome AF: 0.000125

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1402212 Hom.: 0 Cov.: 32 AF XY: 0.00000144 AC XY: 1 AN XY: 695196

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: 0.0000287

Gnomad4 NFE exome AF: 9.17e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000882 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T;.
Eigen	Benign	0.12
Eigen_PC	Benign	-0.027
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.64	T;T
M_CAP	Pathogenic	0.99	D
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.0	M;.
MutationTaster	Benign	0.53	N;N;N
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.40
Sift	Uncertain	0.0060	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.26
MVP		0.84
MPC		2.8
ClinPred		0.50	T
GERP RS		3.8
Varity_R		0.18
gMVP		0.52

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

Other links and lift over

dbSNP: rs200789033; hg19: chr12-52408879;