rs200789033

Positions:

• chr12-52015095-G-A
• chr12-52015095-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_181711.4(TAMALIN):​c.1084G>A​(p.Gly362Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,553,592 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G362D) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0070 (7 hom., cov: 32)
  • Exomes 𝑓: 0.011 (98 hom.)
• Consequence: TAMALIN NM_181711.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005762309).
• BP6: Variant 12-52015095-G-A is Benign according to our data. Variant chr12-52015095-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 221938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAMALIN	NM_181711.4	c.1084G>A	p.Gly362Ser	missense_variant	8/8	ENST00000293662.9
TAMALIN	NM_001271856.2	c.655G>A	p.Gly219Ser	missense_variant	7/7
TAMALIN	XM_005268691.4	c.694G>A	p.Gly232Ser	missense_variant	8/8
TAMALIN	XM_047428439.1	c.694G>A	p.Gly232Ser	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAMALIN	ENST00000293662.9	c.1084G>A	p.Gly362Ser	missense_variant	8/8	1	NM_181711.4	P1

Frequencies

GnomAD3 genomes AF: 0.00699 AC: 1057 AN: 151286 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00335

Gnomad ASJ AF: 0.00579

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0117

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.00482

GnomAD3 exomes AF: 0.00635 AC: 1006 AN: 158510 Hom.: 6 AF XY: 0.00661 AC XY: 587 AN XY: 88766

Gnomad AFR exome AF: 0.00125

Gnomad AMR exome AF: 0.00165

Gnomad ASJ exome AF: 0.00728

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00433

Gnomad FIN exome AF: 0.00941

Gnomad NFE exome AF: 0.0104

Gnomad OTH exome AF: 0.00530

GnomAD4 exome AF: 0.0108 AC: 15175 AN: 1402196 Hom.: 98 Cov.: 32 AF XY: 0.0105 AC XY: 7325 AN XY: 695192

Gnomad4 AFR exome AF: 0.00133

Gnomad4 AMR exome AF: 0.00194

Gnomad4 ASJ exome AF: 0.00777

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00494

Gnomad4 FIN exome AF: 0.00848

Gnomad4 NFE exome AF: 0.0125

Gnomad4 OTH exome AF: 0.00941

GnomAD4 genome AF: 0.00698 AC: 1057 AN: 151396 Hom.: 7 Cov.: 32 AF XY: 0.00649 AC XY: 480 AN XY: 73934

Gnomad4 AFR AF: 0.00174

Gnomad4 AMR AF: 0.00335

Gnomad4 ASJ AF: 0.00579

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0117

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.00477

Alfa AF: 0.00940 Hom.: 2

Bravo AF: 0.00651

ESP6500AA AF: 0.00255 AC: 9

ESP6500EA AF: 0.00619 AC: 47

ExAC AF: 0.00544 AC: 617

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Anophthalmia-microphthalmia syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Paul Sabatier University EA-4555, Paul Sabatier University

Jan 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.20	T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.71	T;T
MetaRNN	Benign	0.0058	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.
MutationTaster	Benign	0.82	N;N;N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.77	N;N
REVEL	Benign	0.10
Sift	Benign	0.082	T;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.66	P;P
Vest4		0.14
MVP		0.68
MPC		1.9
ClinPred		0.0051	T
GERP RS		3.8
Varity_R		0.069
gMVP		0.38

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; COSMIC: COSV99531090; COSMIC: COSV99531090;