Variant 11-62789197-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000333449.9(TMEM179B):c.271G>A(p.Glu91Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TMEM179B
ENST00000333449.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.28

Variant links:

Genes affected

TMEM179B (HGNC:33744): (transmembrane protein 179B) Located in nuclear speck and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

TMEM179B links:

TMEM223 (HGNC:28464): (transmembrane protein 223) Predicted to be involved in nervous system development. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM223 links:

TMEM179B (HGNC:):

TMEM179B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19782105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM179B	NM_199337.3 linkuse as main transcript	c.271G>A	p.Glu91Lys	missense_variant	2/5	ENST00000333449.9	NP_955369.1	Q7Z7N9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM179B	ENST00000333449.9 linkuse as main transcript	c.271G>A	p.Glu91Lys	missense_variant	2/5	1	NM_199337.3	ENSP00000333697.3		Q7Z7N9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251366

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

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

Mar 19, 2024

The c.271G>A (p.E91K) alteration is located in exon 2 (coding exon 2) of the TMEM179B gene. This alteration results from a G to A substitution at nucleotide position 271, causing the glutamic acid (E) at amino acid position 91 to be replaced by a lysine (K). 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

0.22

BayesDel_addAF

Benign

-0.054

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.088

.;T

Eigen

Benign

0.10

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.6

.;M

MutationTaster

Benign

0.92

D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.9

D;N

REVEL

Benign

0.058

Sift

Uncertain

0.012

D;D

Sift4G

Uncertain

0.017

D;D

Polyphen

0.68

.;P

Vest4

0.33

MutPred

0.41

Gain of ubiquitination at E91 (P = 0.0211);Gain of ubiquitination at E91 (P = 0.0211);

MVP

0.31

MPC

0.087

ClinPred

0.93

GERP RS

2.9

Varity_R

0.10

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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