Genetic Variant NM_017799.4:c.107T>C (chr14-56580021-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017799.4(TMEM260):c.107T>C(p.Val36Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000048 in 1,249,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000027 ( 0 hom. )

Consequence

TMEM260
NM_017799.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.63

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.18459544).

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.107T>C	p.Val36Ala	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.107T>C	p.Val36Ala	missense	Exon 1 of 16	ENSP00000261556.6	Q9NX78-1
TMEM260	ENST00000538838.5	TSL:1	c.107T>C	p.Val36Ala	missense	Exon 1 of 13	ENSP00000441934.1	Q9NX78-3
TMEM260	ENST00000539559.6	TSL:1	n.107T>C		non_coding_transcript_exon	Exon 1 of 15	ENSP00000442602.2	F5H7D0

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000579

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:

0.00000273

AC:

AN:

1096920

Hom.:

Cov.:

AF XY:

0.00000579

AC XY:

AN XY:

518382

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23128

American (AMR)

AF:

0.00

AC:

AN:

8632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14390

East Asian (EAS)

AF:

0.0000747

AC:

AN:

26764

South Asian (SAS)

AF:

0.0000502

AC:

AN:

19916

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35186

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3444

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

921570

Other (OTH)

AF:

0.00

AC:

AN:

43890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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:

152306

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41580

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000581

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

0.16

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0076

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.29

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.76

PhyloP100

4.6

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.1

REVEL

Benign

0.16

Sift

Benign

0.15

Sift4G

Benign

0.33

Polyphen

0.36

Vest4

0.55

MutPred

0.40

Loss of stability (P = 0.1123)

MVP

0.18

MPC

0.24

ClinPred

0.61

GERP RS

4.0

PromoterAI

0.035

Neutral

(source)

Varity_R

0.099

gMVP

0.60

Mutation Taster

=49/51

disease causing

(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

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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