7-73865260-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182504.4(TMEM270):​c.340C>T​(p.Leu114Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

TMEM270
NM_182504.4 missense

Scores

2
2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.443
Variant links:
Genes affected
TMEM270 (HGNC:23018): (transmembrane protein 270) 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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1483545).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM270NM_182504.4 linkc.340C>T p.Leu114Phe missense_variant Exon 2 of 3 ENST00000320531.3 NP_872310.2 Q6UE05-1
TMEM270XM_011515785.3 linkc.49C>T p.Leu17Phe missense_variant Exon 2 of 3 XP_011514087.1 Q6UE05
TMEM270XM_017011741.2 linkc.49C>T p.Leu17Phe missense_variant Exon 2 of 3 XP_016867230.1 Q6UE05

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM270ENST00000320531.3 linkc.340C>T p.Leu114Phe missense_variant Exon 2 of 3 1 NM_182504.4 ENSP00000316775.2 Q6UE05-1
TMEM270ENST00000426490.1 linkn.*280C>T non_coding_transcript_exon_variant Exon 3 of 4 5 ENSP00000403621.1 Q6UE05-2
TMEM270ENST00000426490.1 linkn.*280C>T 3_prime_UTR_variant Exon 3 of 4 5 ENSP00000403621.1 Q6UE05-2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152238
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
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
GnomAD3 exomes
AF:
0.00000804
AC:
2
AN:
248778
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135038
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461204
Hom.:
0
Cov.:
68
AF XY:
0.00000550
AC XY:
4
AN XY:
726908
show subpopulations
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:
0.00000809
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152238
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000370
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 05, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.340C>T (p.L114F) alteration is located in exon 2 (coding exon 2) of the WBSCR28 gene. This alteration results from a C to T substitution at nucleotide position 340, causing the leucine (L) at amino acid position 114 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
Benign
0.14
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.020
T
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.56
FATHMM_MKL
Benign
0.0093
N
LIST_S2
Benign
0.45
T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-2.9
D
REVEL
Benign
0.048
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.99
D
Vest4
0.26
MutPred
0.27
Gain of catalytic residue at L114 (P = 0.0966);
MVP
0.072
MPC
0.12
ClinPred
0.35
T
GERP RS
1.0
Varity_R
0.45
gMVP
0.047

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

LitVar

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

Other links and lift over

dbSNP: rs782720817; hg19: chr7-73279590; API