Variant 17-43213058-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145041.4(TMEM106A):c.17C>A(p.Ser6Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000397 in 1,614,208 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 1 hom. )

Consequence

TMEM106A
NM_145041.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83

Variant links:

Genes affected

TMEM106A (HGNC:28288): (transmembrane protein 106A) Predicted to be involved in several processes, including glycoprotein biosynthetic process; positive regulation of cytokine production; and positive regulation of intracellular signal transduction. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM106A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053892583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMEM106A	NM_145041.4 linkuse as main transcript	c.17C>A	p.Ser6Tyr	missense_variant	3/9	ENST00000612339.4	NP_659478.1
TMEM106A	NM_001291586.2 linkuse as main transcript	c.17C>A	p.Ser6Tyr	missense_variant	3/9		NP_001278515.1
TMEM106A	NM_001291588.2 linkuse as main transcript	c.17C>A	p.Ser6Tyr	missense_variant	2/7		NP_001278517.1
TMEM106A	NM_001291587.2 linkuse as main transcript	c.4+13C>A		intron_variant			NP_001278516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM106A	ENST00000612339.4 linkuse as main transcript	c.17C>A	p.Ser6Tyr	missense_variant	3/9	2	NM_145041.4	ENSP00000483246	P1	Q96A25-1

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000334

AC:

AN:

251474

Hom.:

AF XY:

0.000316

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000466

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000399

AC:

583

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000411

AC XY:

299

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000661

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.000406

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.000381

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000412

Hom.:

Bravo

AF:

0.000586

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.000272

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

The c.17C>A (p.S6Y) alteration is located in exon 3 (coding exon 1) of the TMEM106A gene. This alteration results from a C to A substitution at nucleotide position 17, causing the serine (S) at amino acid position 6 to be replaced by a tyrosine (Y). 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

0.13

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.078

T;T;T;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.81

T;.;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.054

T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.9

.;L;.;L

MutationTaster

Benign

0.96

D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.5

.;.;N;.

REVEL

Benign

0.23

Sift

Uncertain

0.014

.;.;D;.

Sift4G

Benign

0.094

T;T;T;T

Polyphen

1.0

.;D;D;D

Vest4

0.69, 0.63

MVP

0.16

ClinPred

0.093

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.49

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

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