Variant 22-17119481-C-G 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.1647G>C(p.Gln549His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000423 in 1,604,040 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 1 hom. )

Consequence

TMEM121B
NM_031890.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0860

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=0.017486423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM121B	NM_031890.4 linkuse as main transcript	c.1647G>C	p.Gln549His	missense_variant	1/1	ENST00000331437.4	NP_114096.1	Q9BXQ6-1
TMEM121B	NM_001163079.2 linkuse as main transcript	c.582G>C	p.Gln194His	missense_variant	2/2		NP_001156551.1	Q9BXQ6-2
TMEM121B	XM_011546124.3 linkuse as main transcript	c.1647G>C	p.Gln549His	missense_variant	1/2		XP_011544426.1	Q9BXQ6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM121B	ENST00000331437.4 linkuse as main transcript	c.1647G>C	p.Gln549His	missense_variant	1/1	6	NM_031890.4	ENSP00000329318.3		Q9BXQ6-1
TMEM121B	ENST00000399875.1 linkuse as main transcript	c.582G>C	p.Gln194His	missense_variant	2/2	2		ENSP00000382764.1		Q9BXQ6-2

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000439

AC:

101

AN:

229930

Hom.:

AF XY:

0.000417

AC XY:

AN XY:

124666

show subpopulations

Gnomad AFR exome

AF:

0.000214

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00105

Gnomad NFE exome

AF:

0.000743

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

AF:

0.000424

AC:

615

AN:

1451902

Hom.:

Cov.:

AF XY:

0.000445

AC XY:

321

AN XY:

721354

show subpopulations

Gnomad4 AFR exome

AF:

0.0000903

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00116

Gnomad4 NFE exome

AF:

0.000485

Gnomad4 OTH exome

AF:

0.000233

GnomAD4 genome

AF:

0.000414

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.000200

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000636

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

May 28, 2024

The c.1647G>C (p.Q549H) alteration is located in exon 1 (coding exon 1) of the CECR6 gene. This alteration results from a G to C substitution at nucleotide position 1647, causing the glutamine (Q) at amino acid position 549 to be replaced by a histidine (H). 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

0.26

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.019

.;T

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.017

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.071

Sift

Benign

0.087

T;T

Sift4G

Uncertain

0.027

D;D

Polyphen

1.0

.;D

Vest4

0.20

MutPred

0.16

.;Gain of glycosylation at P548 (P = 0.1164);

MVP

0.31

ClinPred

0.037

GERP RS

0.82

Varity_R

0.062

gMVP

0.28

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