dbSNP rs1584355393: TMEM270:p.Pro65Ser (chr7-73865113-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182504.4(TMEM270):c.193C>T(p.Pro65Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P65L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TMEM270
NM_182504.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.784

Publications

0 publications found

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]

TMEM270 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13735566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM270	NM_182504.4 link	c.193C>T	p.Pro65Ser	missense_variant	Exon 2 of 3	ENST00000320531.3	NP_872310.2	Q6UE05-1
TMEM270	XM_011515785.3 link	c.-99C>T		5_prime_UTR_variant	Exon 2 of 3		XP_011514087.1	Q6UE05
TMEM270	XM_017011741.2 link	c.-99C>T		5_prime_UTR_variant	Exon 2 of 3		XP_016867230.1	Q6UE05

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMEM270	ENST00000320531.3 link	c.193C>T	p.Pro65Ser	missense_variant	Exon 2 of 3	1	NM_182504.4	ENSP00000316775.2	Q6UE05-1
TMEM270	ENST00000426490.1 link	n.*133C>T		non_coding_transcript_exon_variant	Exon 3 of 4	5		ENSP00000403621.1	Q6UE05-2
TMEM270	ENST00000426490.1 link	n.*133C>T		3_prime_UTR_variant	Exon 3 of 4	5		ENSP00000403621.1	Q6UE05-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1443108

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

715546

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32954

American (AMR)

AF:

0.00

AC:

AN:

42574

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25110

East Asian (EAS)

AF:

0.00

AC:

AN:

39392

South Asian (SAS)

AF:

0.00

AC:

AN:

84030

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101018

Other (OTH)

AF:

0.0000168

AC:

AN:

59396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 07, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.193C>T (p.P65S) 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 193, causing the proline (P) at amino acid position 65 to be replaced by a serine (S). 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

0.10

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.7

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.027

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.39

M_CAP

Benign

0.018

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.99

PhyloP100

0.78

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-5.7

REVEL

Benign

0.012

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.39

Vest4

0.20

MutPred

0.47

Loss of glycosylation at P65 (P = 0.275);

MVP

0.099

MPC

0.017

ClinPred

0.24

GERP RS

1.4

Varity_R

0.21

gMVP

0.071

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over