Variant 6-75265242-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000230461.11(TMEM30A):c.442A>G(p.Ser148Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TMEM30A
ENST00000230461.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

Variant links:

Genes affected

TMEM30A (HGNC:16667): (transmembrane protein 30A) Enables aminophospholipid flippase activity. Involved in several processes, including phospholipid transport; positive regulation of transport; and xenobiotic transmembrane transport. Located in endoplasmic reticulum and plasma membrane. Part of phospholipid-translocating ATPase complex. [provided by Alliance of Genome Resources, Apr 2022]

TMEM30A links:

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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=0.16991681).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM30A	NM_018247.4 linkuse as main transcript	c.442A>G	p.Ser148Gly	missense_variant	3/7	ENST00000230461.11	NP_060717.1
TMEM30A	NM_001143958.2 linkuse as main transcript	c.334A>G	p.Ser112Gly	missense_variant	2/6		NP_001137430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM30A	ENST00000230461.11 linkuse as main transcript	c.442A>G	p.Ser148Gly	missense_variant	3/7	1	NM_018247.4	ENSP00000230461	P1	Q9NV96-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1446398

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

720222

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:

0.00000182

Gnomad4 OTH exome

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2023

The c.442A>G (p.S148G) alteration is located in exon 3 (coding exon 3) of the TMEM30A gene. This alteration results from a A to G substitution at nucleotide position 442, causing the serine (S) at amino acid position 148 to be replaced by a glycine (G). 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

0.082

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.;.;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.66

T;T;T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;.;.;.

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Benign

0.083

Sift

Benign

0.062

T;T;T;T

Sift4G

Benign

0.082

T;T;T;.

Polyphen

0.0

B;.;B;.

Vest4

0.074

MutPred

0.41

Gain of glycosylation at S147 (P = 0.0299);.;.;.;

MVP

0.63

MPC

0.50

ClinPred

0.20

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.22

gMVP

0.50

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over