14-56580030-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017799.4(TMEM260):ā€‹c.116T>Cā€‹(p.Val39Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,250,562 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 (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V39E) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.00032 ( 0 hom., cov: 33)
Exomes š‘“: 0.00016 ( 0 hom. )

Consequence

TMEM260
NM_017799.4 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.16
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.016960263).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TMEM260NM_017799.4 linkuse as main transcriptc.116T>C p.Val39Ala missense_variant 1/16 ENST00000261556.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TMEM260ENST00000261556.11 linkuse as main transcriptc.116T>C p.Val39Ala missense_variant 1/162 NM_017799.4 P1Q9NX78-1

Frequencies

GnomAD3 genomes
AF:
0.000322
AC:
49
AN:
152176
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.0164
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000127
AC:
3
AN:
23664
Hom.:
0
AF XY:
0.0000872
AC XY:
1
AN XY:
11468
show subpopulations
Gnomad AFR exome
AF:
0.000557
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000103
Gnomad NFE exome
AF:
0.000105
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000161
AC:
177
AN:
1098268
Hom.:
0
Cov.:
30
AF XY:
0.000154
AC XY:
80
AN XY:
519128
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000343
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000844
Gnomad4 NFE exome
AF:
0.000182
Gnomad4 OTH exome
AF:
0.0000683
GnomAD4 genome
AF:
0.000322
AC:
49
AN:
152294
Hom.:
0
Cov.:
33
AF XY:
0.000363
AC XY:
27
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00118
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000351
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000956
AC:
9

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 submitterclinical testingAmbry GeneticsJun 05, 2023The c.116T>C (p.V39A) alteration is located in exon 1 (coding exon 1) of the TMEM260 gene. This alteration results from a T to C substitution at nucleotide position 116, causing the valine (V) at amino acid position 39 to be replaced by an alanine (A). 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
Benign
0.18
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.19
T;.
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.078
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.57
T;T
M_CAP
Pathogenic
0.50
D
MetaRNN
Benign
0.017
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.9
M;M
MutationTaster
Benign
0.87
D;D;D
PrimateAI
Pathogenic
0.82
D
PROVEAN
Uncertain
-2.4
N;N
REVEL
Benign
0.14
Sift
Uncertain
0.015
D;D
Sift4G
Uncertain
0.023
D;D
Polyphen
0.16
B;.
Vest4
0.47
MutPred
0.43
Loss of stability (P = 0.0525);Loss of stability (P = 0.0525);
MVP
0.35
MPC
0.036
ClinPred
0.11
T
GERP RS
5.1
Varity_R
0.21
gMVP
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs575803718; hg19: chr14-57046748; API