Genetic Variant TMEM260:p.Val18Glu (chr14-56579967-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017799.4(TMEM260):c.53T>A(p.Val18Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,242,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

TMEM260
NM_017799.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.71

Publications

0 publications found

Variant links:

Genes affected

TMEM260 (HGNC:20185): (transmembrane protein 260) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM260 Gene-Disease associations (from GenCC):

structural heart defects and renal anomalies syndrome
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P

TMEM260 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06266713).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017799.4. 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
	TMEM260	NM_017799.4	MANE Select	c.53T>A	p.Val18Glu	missense	Exon 1 of 16	NP_060269.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM260	ENST00000261556.11	TSL:2 MANE Select	c.53T>A	p.Val18Glu	missense	Exon 1 of 16	ENSP00000261556.6	Q9NX78-1
TMEM260	ENST00000538838.5	TSL:1	c.53T>A	p.Val18Glu	missense	Exon 1 of 13	ENSP00000441934.1	Q9NX78-3
TMEM260	ENST00000539559.6	TSL:1	n.53T>A		non_coding_transcript_exon	Exon 1 of 15	ENSP00000442602.2	F5H7D0

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000119

AC:

AN:

1089786

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

515084

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23000

American (AMR)

AF:

0.00

AC:

AN:

8454

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14376

East Asian (EAS)

AF:

0.000150

AC:

AN:

26602

South Asian (SAS)

AF:

0.00

AC:

AN:

19878

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29750

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3050

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

920936

Other (OTH)

AF:

0.000206

AC:

AN:

43740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

0.0000197

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41532

American (AMR)

AF:

0.0000653

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68000

Other (OTH)

AF:

0.000475

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

Asia WGS

AF:

0.00462

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.0046

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.50

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

-2.7

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.34

REVEL

Benign

0.036

Sift

Uncertain

0.022

Sift4G

Benign

0.14

Polyphen

0.0

Vest4

0.15

MutPred

0.24

Gain of disorder (P = 0.0299)

MVP

0.014

MPC

0.042

ClinPred

0.32

GERP RS

-6.5

PromoterAI

0.010

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.12

gMVP

0.60

Mutation Taster

=98/2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over