Variant chr14-56580072-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017799.4(TMEM260):c.158C>T(p.Ser53Phe) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000657 in 152,242 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMEM260
NM_017799.4 missense, splice_region

Scores

Splicing: ADA: 0.8670

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.73

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM260	NM_017799.4 linkuse as main transcript	c.158C>T	p.Ser53Phe	missense_variant, splice_region_variant	1/16	ENST00000261556.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM260	ENST00000261556.11 linkuse as main transcript	c.158C>T	p.Ser53Phe	missense_variant, splice_region_variant	1/16	2	NM_017799.4	P1	Q9NX78-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152242

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:

0.000193

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1099370

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

519492

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2023

The c.158C>T (p.S53F) alteration is located in exon 1 (coding exon 1) of the TMEM260 gene. This alteration results from a C to T substitution at nucleotide position 158, causing the serine (S) at amino acid position 53 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

T;.

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.94

D;D

M_CAP

Pathogenic

0.49

MetaRNN

Uncertain

0.64

D;D

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.7

M;M

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-4.1

D;D

REVEL

Benign

0.29

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.77

P;.

Vest4

0.69

MutPred

0.39

Loss of disorder (P = 0.002);Loss of disorder (P = 0.002);

MVP

0.53

MPC

0.20

ClinPred

0.99

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.59

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.87

dbscSNV1_RF

Benign

0.56

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over