Genetic Variant TMEM270:p.Arg20Ser (chr7-73861254-G-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.60G>T(p.Arg20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TMEM270
NM_182504.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.433

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:

ENSG00000299575 (HGNC:):

ENSG00000299575 links:

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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=0.20750433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM270	NM_182504.4 link	c.60G>T	p.Arg20Ser	missense_variant	Exon 1 of 3	ENST00000320531.3	NP_872310.2	Q6UE05-1
TMEM270	XM_017011741.2 link	c.-220+177G>T		intron_variant	Intron 1 of 2		XP_016867230.1	Q6UE05

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMEM270	ENST00000320531.3 link	c.60G>T	p.Arg20Ser	missense_variant	Exon 1 of 3	1	NM_182504.4	ENSP00000316775.2	Q6UE05-1
TMEM270	ENST00000426490.1 link	n.60G>T		non_coding_transcript_exon_variant	Exon 1 of 4	5		ENSP00000403621.1	Q6UE05-2
ENSG00000299575	ENST00000764718.1 link	n.-202C>A		upstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248654

AF XY:

0.00000740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459942

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726218

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33432

American (AMR)

AF:

0.0000224

AC:

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.00

AC:

AN:

86186

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53240

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5584

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110732

Other (OTH)

AF:

0.0000166

AC:

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 15, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.60G>T (p.R20S) alteration is located in exon 1 (coding exon 1) of the WBSCR28 gene. This alteration results from a G to T substitution at nucleotide position 60, causing the arginine (R) at amino acid position 20 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

Uncertain

0.49

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.022

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.59

M_CAP

Benign

0.0053

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

PhyloP100

0.43

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.074

Sift

Benign

0.12

Sift4G

Uncertain

0.021

Polyphen

0.93

Vest4

0.23

MutPred

0.39

Gain of catalytic residue at L16 (P = 0.1163);

MVP

0.095

MPC

0.082

ClinPred

0.93

GERP RS

2.3

PromoterAI

-0.0056

Neutral

(source)

Varity_R

0.21

gMVP

0.11

Mutation Taster

=95/5

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