rs774382007

Variant names:

• chr2-192184416-C-A
• NM_016192.4:c.350G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-192184416-C-A
• chr2-192184416-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016192.4(TMEFF2):​c.350G>T​(p.Arg117Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,198 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R117Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TMEFF2 NM_016192.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.73

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEFF2	NM_016192.4	c.350G>T	p.Arg117Leu	missense_variant	Exon 3 of 10	ENST00000272771.10	NP_057276.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEFF2	ENST00000272771.10	c.350G>T	p.Arg117Leu	missense_variant	Exon 3 of 10	1	NM_016192.4	ENSP00000272771.5
TMEFF2	ENST00000392314.5	c.350G>T	p.Arg117Leu	missense_variant	Exon 3 of 10	1		ENSP00000376128.1
TMEFF2	ENST00000409056.3	c.350G>T	p.Arg117Leu	missense_variant	Exon 3 of 4	1		ENSP00000386871.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461198 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726914

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	.;T;.
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.9	L;L;L
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D;D;D
Sift4G	Benign	0.16	T;T;D
Polyphen		1.0, 0.99	.;D;D
Vest4		0.65
MutPred		0.66		Loss of ubiquitination at K122 (P = 0.0509);Loss of ubiquitination at K122 (P = 0.0509);Loss of ubiquitination at K122 (P = 0.0509);
MVP		0.44
MPC		1.6
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.61
gMVP		0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-193049142;