Genetic Variant NM_003692.5:c.37C>T (chr9-100473581-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

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

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35288846).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003692.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEFF1	NM_003692.5	MANE Select	c.37C>T	p.Pro13Ser	missense	Exon 1 of 10	NP_003683.2
	MSANTD3-TMEFF1	NM_001198812.1		c.419-25184C>T		intron	N/A	NP_001185741.1	Q8IYR6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEFF1	ENST00000374879.5	TSL:1 MANE Select	c.37C>T	p.Pro13Ser	missense	Exon 1 of 10	ENSP00000364013.4	Q8IYR6-1
MSANTD3-TMEFF1	ENST00000502978.1	TSL:2	c.80-25184C>T		intron	N/A	ENSP00000424768.2
TMEFF1	ENST00000906124.1		c.37C>T	p.Pro13Ser	missense	Exon 1 of 11	ENSP00000576183.1

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

African (AFR)

AF:

0.00

AC:

AN:

30082

American (AMR)

AF:

0.00

AC:

AN:

36476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24738

East Asian (EAS)

AF:

0.00

AC:

AN:

35080

South Asian (SAS)

AF:

0.00

AC:

AN:

77940

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5270

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1080944

Other (OTH)

AF:

0.00

AC:

AN:

57810

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

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

PhyloP100

1.6

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

PromoterAI

-0.047

Neutral

(source)

Varity_R

0.065

gMVP

0.14

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over