Genetic Variant TMEM260:n.*1204G>A (chr14-56647667-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000539559.6(TMEM260):n.*1204G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 675,144 control chromosomes in the GnomAD database, including 3,491 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1449 hom., cov: 33)

Exomes 𝑓: 0.069 ( 2042 hom. )

Consequence

TMEM260
ENST00000539559.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.494

Publications

20 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: Labcorp Genetics (formerly Invitae), G2P

TMEM260 links:

ENSG00000258428 (HGNC:):

ENSG00000258428 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM260	NM_017799.4 link	c.*170G>A		3_prime_UTR_variant	Exon 16 of 16	ENST00000261556.11	NP_060269.3	Q9NX78-1B3KN73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM260	ENST00000261556.11 link	c.*170G>A		3_prime_UTR_variant	Exon 16 of 16	2	NM_017799.4	ENSP00000261556.6		Q9NX78-1

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17230

AN:

152008

Hom.:

1439

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.0363

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.0831

Gnomad EAS

AF:

0.298

Gnomad SAS

AF:

0.0708

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0479

Gnomad OTH

AF:

0.0898

GnomAD4 exome

AF:

0.0686

AC:

35866

AN:

523018

Hom.:

2042

Cov.:

AF XY:

0.0676

AC XY:

18104

AN XY:

267798

show subpopulations

African (AFR)

AF:

0.195

AC:

2253

AN:

11572

American (AMR)

AF:

0.181

AC:

2182

AN:

12036

Ashkenazi Jewish (ASJ)

AF:

0.0758

AC:

992

AN:

13090

East Asian (EAS)

AF:

0.246

AC:

6602

AN:

26892

South Asian (SAS)

AF:

0.0687

AC:

2505

AN:

36472

European-Finnish (FIN)

AF:

0.101

AC:

2817

AN:

27830

Middle Eastern (MID)

AF:

0.0713

AC:

151

AN:

2118

European-Non Finnish (NFE)

AF:

0.0438

AC:

16020

AN:

365490

Other (OTH)

AF:

0.0852

AC:

2344

AN:

27518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1531

3061

4592

6122

7653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

394

788

1182

1576

1970

<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:

0.113

AC:

17262

AN:

152126

Hom.:

1449

Cov.:

AF XY:

0.117

AC XY:

8682

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.195

AC:

8099

AN:

41488

American (AMR)

AF:

0.153

AC:

2339

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0831

AC:

288

AN:

3464

East Asian (EAS)

AF:

0.298

AC:

1540

AN:

5170

South Asian (SAS)

AF:

0.0701

AC:

338

AN:

4824

European-Finnish (FIN)

AF:

0.109

AC:

1155

AN:

10582

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0478

AC:

3253

AN:

67994

Other (OTH)

AF:

0.0907

AC:

192

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

749

1498

2246

2995

3744

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

178

356

534

712

890

<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:

0.0740

Hom.:

993

Bravo

AF:

0.123

Asia WGS

AF:

0.190

AC:

659

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.15

(source)

DANN

Benign

0.47

PhyloP100

-0.49

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over