Variant 22-17120349-G-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_031890.4(TMEM121B):c.779C>T(p.Ala260Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,531,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

TMEM121B
NM_031890.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.312

Variant links:

Genes affected

TMEM121B (HGNC:1844): (transmembrane protein 121B)

TMEM121B 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=0.033501446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMEM121B	NM_031890.4 linkuse as main transcript	c.779C>T	p.Ala260Val	missense_variant	1/1	ENST00000331437.4	NP_114096.1
TMEM121B	XM_011546124.3 linkuse as main transcript	c.779C>T	p.Ala260Val	missense_variant	1/2		XP_011544426.1
TMEM121B	NM_001163079.2 linkuse as main transcript	c.-81-206C>T		intron_variant			NP_001156551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM121B	ENST00000331437.4 linkuse as main transcript	c.779C>T	p.Ala260Val	missense_variant	1/1		NM_031890.4	ENSP00000329318	P1	Q9BXQ6-1
TMEM121B	ENST00000399875.1 linkuse as main transcript	c.-81-206C>T		intron_variant		2		ENSP00000382764		Q9BXQ6-2

Frequencies

GnomAD3 genomes

AF:

0.000259

AC:

AN:

150620

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000629

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

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:

0.000133

Gnomad OTH

AF:

0.000484

GnomAD3 exomes

AF:

0.000154

AC:

AN:

174904

Hom.:

AF XY:

0.000130

AC XY:

AN XY:

99944

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000725

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000726

Gnomad OTH exome

AF:

0.000500

GnomAD4 exome

AF:

0.000113

AC:

156

AN:

1380630

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

687238

show subpopulations

Gnomad4 AFR exome

AF:

0.000414

Gnomad4 AMR exome

AF:

0.000599

Gnomad4 ASJ exome

AF:

0.0000411

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000862

Gnomad4 OTH exome

AF:

0.000405

GnomAD4 genome

AF:

0.000259

AC:

AN:

150620

Hom.:

Cov.:

AF XY:

0.000218

AC XY:

AN XY:

73512

show subpopulations

Gnomad4 AFR

AF:

0.000629

Gnomad4 AMR

AF:

0.000198

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.000484

Alfa

AF:

0.000147

Hom.:

Bravo

AF:

0.000408

ESP6500AA

AF:

0.000490

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000103

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

Oct 04, 2022

The c.779C>T (p.A260V) alteration is located in exon 1 (coding exon 1) of the CECR6 gene. This alteration results from a C to T substitution at nucleotide position 779, causing the alanine (A) at amino acid position 260 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.5

DANN

Benign

0.94

DEOGEN2

Benign

0.0069

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.33

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.58

D;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.17

REVEL

Benign

0.015

Sift

Benign

0.19

Sift4G

Uncertain

0.053

Polyphen

0.0

Vest4

0.023

MVP

0.17

ClinPred

0.013

GERP RS

-1.7

Varity_R

0.035

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