Genetic Variant TMA16:p.Arg12Trp (chr4-163507063-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018352.3(TMA16):c.34C>T(p.Arg12Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000113 in 1,593,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R12Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

TMA16
NM_018352.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.70

Variant links:

Genes affected

TMA16 (HGNC:25638): (translation machinery associated 16 homolog) Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TMA16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08031699).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMA16	NM_018352.3 link	c.34C>T	p.Arg12Trp	missense_variant	Exon 2 of 7	ENST00000358572.10	NP_060822.2	Q96EY4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMA16	ENST00000358572.10 link	c.34C>T	p.Arg12Trp	missense_variant	Exon 2 of 7	1	NM_018352.3	ENSP00000351380.5		Q96EY4

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151452

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000227

AC:

AN:

220648

Hom.:

AF XY:

0.0000422

AC XY:

AN XY:

118386

show subpopulations

Gnomad AFR exome

AF:

0.0000767

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000375

Gnomad FIN exome

AF:

0.0000497

Gnomad NFE exome

AF:

0.0000205

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1441606

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

714706

show subpopulations

Gnomad4 AFR exome

AF:

0.0000603

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000390

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

0.00000817

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151568

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74020

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000249

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.34C>T (p.R12W) alteration is located in exon 2 (coding exon 2) of the TMA16 gene. This alteration results from a C to T substitution at nucleotide position 34, causing the arginine (R) at amino acid position 12 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.070

T;T;T;.

Eigen

Benign

0.030

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.78

T;T;T;T

M_CAP

Benign

0.0090

MetaRNN

Benign

0.080

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.49

N;.;.;.

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-3.0

D;D;D;D

REVEL

Benign

0.037

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Benign

0.10

T;T;T;T

Polyphen

0.0090

B;.;.;.

Vest4

0.33

MVP

0.24

MPC

0.12

ClinPred

0.36

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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