12-52015095-G-C

Variant names:

• chr12-52015095-G-C
• rs200789033
• NM_181711.4:c.1084G>C

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.947
• Publications: 0 publications found

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

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

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAMALIN	NM_181711.4	c.1084G>C	p.Gly362Arg	missense_variant	Exon 8 of 8	ENST00000293662.9	NP_859062.1
TAMALIN	NM_001271856.2	c.655G>C	p.Gly219Arg	missense_variant	Exon 7 of 7		NP_001258785.1
TAMALIN	XM_005268691.4	c.694G>C	p.Gly232Arg	missense_variant	Exon 8 of 8		XP_005268748.1
TAMALIN	XM_047428439.1	c.694G>C	p.Gly232Arg	missense_variant	Exon 7 of 7		XP_047284395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAMALIN	ENST00000293662.9	c.1084G>C	p.Gly362Arg	missense_variant	Exon 8 of 8	1	NM_181711.4	ENSP00000293662.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1402212 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 695196

African (AFR) AF: 0.00 AC: 0 AN: 31688

American (AMR) AF: 0.00 AC: 0 AN: 37614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24968

East Asian (EAS) AF: 0.0000271 AC: 1 AN: 36914

South Asian (SAS) AF: 0.00 AC: 0 AN: 81782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5470

European-Non Finnish (NFE) AF: 9.17e-7 AC: 1 AN: 1090504

Other (OTH) AF: 0.00 AC: 0 AN: 58480

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.48	T;.
Eigen	Benign	0.10
Eigen_PC	Benign	-0.040
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.73	T;T
M_CAP	Pathogenic	0.99	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.0	M;.
PhyloP100		0.95
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-2.2	N;N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0040	D;D
Sift4G	Pathogenic	0.0	D;D
Vest4		0.18
ClinPred		0.92	D
GERP RS		3.8
Varity_R		0.11
gMVP		0.47
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs200789033; hg19: chr12-52408879;