Variant 2-191950393-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016192.4(TMEFF2):c.1043G>T(p.Ser348Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000212 in 1,461,790 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: 31)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

TMEFF2
NM_016192.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.89

Variant links:

Genes affected

TMEFF2 (HGNC:11867): (transmembrane protein with EGF like and two follistatin like domains 2) This gene encodes a member of the tomoregulin family of transmembrane proteins. This protein has been shown to function as both an oncogene and a tumor suppressor depending on the cellular context and may regulate prostate cancer cell invasion. Multiple soluble forms of this protein have been identified that arise from both an alternative splice variant and ectodomain shedding. Additionally, this gene has been found to be hypermethylated in multiple cancer types. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

TMEFF2 links:

CAVIN2-AS1 (HGNC:):

CAVIN2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2969514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEFF2	NM_016192.4 linkuse as main transcript	c.1043G>T	p.Ser348Ile	missense_variant	10/10	ENST00000272771.10	NP_057276.2	Q9UIK5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEFF2	ENST00000272771.10 linkuse as main transcript	c.1043G>T	p.Ser348Ile	missense_variant	10/10	1	NM_016192.4	ENSP00000272771.5	Q9UIK5-1
TMEFF2	ENST00000392314.5 linkuse as main transcript	c.*59G>T		3_prime_UTR_variant	10/10	1		ENSP00000376128.1	Q9UIK5-2
CAVIN2-AS1	ENST00000424116.7 linkuse as main transcript	n.239-84301C>A		intron_variant		2
CAVIN2-AS1	ENST00000428980.6 linkuse as main transcript	n.499+27349C>A		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251376

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135850

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:

0.0000352

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461790

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727192

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000675

Hom.:

Bravo

AF:

0.0000113

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

Apr 01, 2024

The c.1043G>T (p.S348I) alteration is located in exon 10 (coding exon 10) of the TMEFF2 gene. This alteration results from a G to T substitution at nucleotide position 1043, causing the serine (S) at amino acid position 348 to be replaced by an isoleucine (I). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.023

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.34

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-1.9

REVEL

Benign

0.13

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.059

Polyphen

0.43

Vest4

0.32

MutPred

0.26

Loss of disorder (P = 0.0047);

MVP

0.85

MPC

0.91

ClinPred

0.24

GERP RS

5.8

Varity_R

0.44

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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