Variant 6-75260845-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000230461.11(TMEM30A):c.520A>G(p.Ile174Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,840 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TMEM30A
ENST00000230461.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.88

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM30A	NM_018247.4 linkuse as main transcript	c.520A>G	p.Ile174Val	missense_variant	4/7	ENST00000230461.11	NP_060717.1
TMEM30A	NM_001143958.2 linkuse as main transcript	c.412A>G	p.Ile138Val	missense_variant	3/6		NP_001137430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM30A	ENST00000230461.11 linkuse as main transcript	c.520A>G	p.Ile174Val	missense_variant	4/7	1	NM_018247.4	ENSP00000230461	P1	Q9NV96-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000424

AC:

AN:

236074

Hom.:

AF XY:

0.00000780

AC XY:

AN XY:

128154

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000343

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1444840

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718954

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000255

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:

0.00

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

Dec 14, 2023

The c.520A>G (p.I174V) alteration is located in exon 4 (coding exon 4) of the TMEM30A gene. This alteration results from a A to G substitution at nucleotide position 520, causing the isoleucine (I) at amino acid position 174 to be replaced by a valine (V). 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

0.17

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.;.;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D;D;D

M_CAP

Benign

0.0072

MetaRNN

Uncertain

0.68

D;D;D;D

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.5

M;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.90

N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.12

T;T;T;T

Sift4G

Benign

0.13

T;T;T;.

Polyphen

0.94

P;.;P;.

Vest4

0.55

MutPred

0.78

Loss of helix (P = 0.1706);.;.;.;

MVP

0.67

MPC

1.3

ClinPred

0.79

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.73

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over