Variant 9-100473581-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003692.5(TMEFF1):c.37C>T(p.Pro13Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMEFF1
NM_003692.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

Variant links:

Genes affected

TMEFF1 (HGNC:11866): (transmembrane protein with EGF like and two follistatin like domains 1) Predicted to enable signaling receptor binding activity. Predicted to be involved in animal organ morphogenesis; neuron projection development; and tissue development. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEFF1 links:

MSANTD3-TMEFF1 (HGNC:38838): (MSANTD3-TMEFF1 readthrough) This locus represents naturally occurring read-through transcription from the neighboring MSANTD3 (Myb/SANT-like DNA-binding domain containing 3) and TMEFF1 (transmembrane protein with EGF-like and two follistatin-like domains 1) genes. The read-through transcript encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Aug 2013]

MSANTD3-TMEFF1 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=0.35288846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEFF1	NM_003692.5 link	c.37C>T	p.Pro13Ser	missense_variant	1/10	ENST00000374879.5	NP_003683.2	Q8IYR6-1
MSANTD3-TMEFF1	NM_001198812.1 link	c.419-25184C>T		intron_variant			NP_001185741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEFF1	ENST00000374879.5 link	c.37C>T	p.Pro13Ser	missense_variant	1/10	1	NM_003692.5	ENSP00000364013.4		Q8IYR6-1
MSANTD3-TMEFF1	ENST00000502978.1 link	c.80-25184C>T		intron_variant		2		ENSP00000424768.2		A0A0A6YYJ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1395872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689898

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 20, 2024

The c.37C>T (p.P13S) alteration is located in exon 1 (coding exon 1) of the TMEFF1 gene. This alteration results from a C to T substitution at nucleotide position 37, causing the proline (P) at amino acid position 13 to be replaced by a serine (S). 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

0.10

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

0.10

Eigen_PC

Benign

0.039

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.54

M_CAP

Pathogenic

1.0

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.66

MutationAssessor

Benign

-0.81

PROVEAN

Benign

0.38

REVEL

Benign

0.11

Sift

Benign

0.039

Sift4G

Benign

0.33

Polyphen

0.91

Vest4

0.18

MutPred

0.32

Gain of phosphorylation at P13 (P = 0.0401);

MVP

0.32

MPC

0.70

ClinPred

0.72

GERP RS

3.1

Varity_R

0.065

gMVP

0.14

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over