Variant 22-17120553-G-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_031890.4(TMEM121B):c.575C>A(p.Pro192His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000331 in 1,511,424 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 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

TMEM121B
NM_031890.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.21

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=0.020341426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM121B	NM_031890.4 linkuse as main transcript	c.575C>A	p.Pro192His	missense_variant	1/1	ENST00000331437.4	NP_114096.1	Q9BXQ6-1
TMEM121B	XM_011546124.3 linkuse as main transcript	c.575C>A	p.Pro192His	missense_variant	1/2		XP_011544426.1	Q9BXQ6-1
TMEM121B	NM_001163079.2 linkuse as main transcript	c.-81-410C>A		intron_variant			NP_001156551.1	Q9BXQ6-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM121B	ENST00000331437.4 linkuse as main transcript	c.575C>A	p.Pro192His	missense_variant	1/1	6	NM_031890.4	ENSP00000329318.3		Q9BXQ6-1
TMEM121B	ENST00000399875.1 linkuse as main transcript	c.-81-410C>A		intron_variant		2		ENSP00000382764.1		Q9BXQ6-2

Frequencies

GnomAD3 genomes

AF:

0.000160

AC:

AN:

150422

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000581

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000245

AC:

AN:

122256

Hom.:

AF XY:

0.00

AC XY:

AN XY:

68634

show subpopulations

Gnomad AFR exome

AF:

0.000795

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000191

AC:

AN:

1361002

Hom.:

Cov.:

AF XY:

0.0000149

AC XY:

AN XY:

672992

show subpopulations

Gnomad4 AFR exome

AF:

0.000801

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000309

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.37e-7

Gnomad4 OTH exome

AF:

0.0000177

GnomAD4 genome

AF:

0.000160

AC:

AN:

150422

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

AN XY:

73392

show subpopulations

Gnomad4 AFR

AF:

0.000581

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000261

ExAC

AF:

0.0000467

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 12, 2024

The c.575C>A (p.P192H) alteration is located in exon 1 (coding exon 1) of the CECR6 gene. This alteration results from a C to A substitution at nucleotide position 575, causing the proline (P) at amino acid position 192 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

0.15

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0096

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.35

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.0

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.31

REVEL

Benign

0.045

Sift

Benign

0.15

Sift4G

Benign

0.71

Polyphen

0.047

Vest4

0.13

MutPred

0.21

Loss of glycosylation at P192 (P = 0.018);

MVP

0.18

ClinPred

0.037

GERP RS

2.4

Varity_R

0.071

gMVP

0.080

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