Variant chr14-105529766-C-T 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_025268.4(TMEM121):c.932C>T(p.Ser311Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,485,962 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 0.0011 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0014 ( 1 hom. )

Consequence

TMEM121
NM_025268.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

Variant links:

Genes affected

TMEM121 (HGNC:20511): (transmembrane protein 121) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM121 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=0.012311816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM121	NM_025268.4 linkuse as main transcript	c.932C>T	p.Ser311Leu	missense_variant	2/2	ENST00000392519.7	NP_079544.1	Q9BTD3
TMEM121	NM_001331238.2 linkuse as main transcript	c.932C>T	p.Ser311Leu	missense_variant	2/2		NP_001318167.1	Q9BTD3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM121	ENST00000392519.7 linkuse as main transcript	c.932C>T	p.Ser311Leu	missense_variant	2/2	1	NM_025268.4	ENSP00000376304.2		Q9BTD3

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

160

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00879

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000771

AC:

AN:

80438

Hom.:

AF XY:

0.000793

AC XY:

AN XY:

45410

show subpopulations

Gnomad AFR exome

AF:

0.000304

Gnomad AMR exome

AF:

0.000613

Gnomad ASJ exome

AF:

0.00158

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000413

Gnomad NFE exome

AF:

0.00130

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

AF:

0.00142

AC:

1889

AN:

1333650

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

952

AN XY:

657272

show subpopulations

Gnomad4 AFR exome

AF:

0.000283

Gnomad4 AMR exome

AF:

0.000705

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000708

Gnomad4 FIN exome

AF:

0.000327

Gnomad4 NFE exome

AF:

0.00166

Gnomad4 OTH exome

AF:

0.00110

GnomAD4 genome

AF:

0.00105

AC:

160

AN:

152312

Hom.:

Cov.:

AF XY:

0.000913

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.00169

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00134

Hom.:

Bravo

AF:

0.000967

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ExAC

AF:

0.000391

AC:

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

Nov 02, 2021

The c.932C>T (p.S311L) alteration is located in exon 2 (coding exon 1) of the TMEM121 gene. This alteration results from a C to T substitution at nucleotide position 932, causing the serine (S) at amino acid position 311 to be replaced by a leucine (L). 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

0.12

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.070

T;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.67

.;T

M_CAP

Pathogenic

0.60

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.84

N;N

REVEL

Benign

0.034

Sift

Uncertain

0.0040

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.95

P;P

Vest4

0.41

MVP

0.061

MPC

2.0

ClinPred

0.032

GERP RS

3.4

Varity_R

0.12

gMVP

0.39

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