chr9-100473555-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003692.5(TMEFF1):c.11C>T(p.Ala4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000812 in 1,526,254 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A4T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000083 ( 0 hom. )

Consequence

TMEFF1
NM_003692.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0130

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10632563).

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.11C>T	p.Ala4Val	missense	Exon 1 of 10	NP_003683.2
	MSANTD3-TMEFF1	NM_001198812.1		c.419-25210C>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.11C>T	p.Ala4Val	missense	Exon 1 of 10	ENSP00000364013.4	Q8IYR6-1
MSANTD3-TMEFF1	ENST00000502978.1	TSL:2	c.80-25210C>T		intron	N/A	ENSP00000424768.2
TMEFF1	ENST00000906124.1		c.11C>T	p.Ala4Val	missense	Exon 1 of 11	ENSP00000576183.1

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

151964

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000479

AC:

AN:

125142

AF XY:

0.0000721

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000127

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000830

AC:

114

AN:

1374290

Hom.:

Cov.:

AF XY:

0.0000840

AC XY:

AN XY:

678458

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28866

American (AMR)

AF:

0.00

AC:

AN:

33920

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24230

East Asian (EAS)

AF:

0.00

AC:

AN:

33578

South Asian (SAS)

AF:

0.00

AC:

AN:

76412

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44098

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4750

European-Non Finnish (NFE)

AF:

0.000103

AC:

110

AN:

1071534

Other (OTH)

AF:

0.0000703

AC:

AN:

56902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000658

AC:

AN:

151964

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5120

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67968

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000365

AC:

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

Uncertain

0.36

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.12

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.47

M_CAP

Pathogenic

0.94

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.013

PROVEAN

Benign

-0.010

REVEL

Benign

0.086

Sift

Benign

0.89

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.17

MutPred

0.14

Loss of disorder (P = 0.0531)

MVP

0.58

MPC

0.58

ClinPred

0.078

GERP RS

0.75

PromoterAI

-0.052

Neutral

(source)

Varity_R

0.027

gMVP

0.27

Mutation Taster

=90/10

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over