Variant 7-1547173-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001097620.2(TMEM184A):c.1021G>A(p.Ala341Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000623 in 1,444,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

TMEM184A
NM_001097620.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.90

Variant links:

Genes affected

TMEM184A (HGNC:28797): (transmembrane protein 184A) Predicted to enable heparin binding activity. Predicted to act upstream of or within germ-line sex determination; regulation of protein localization; and regulation of secretion. Predicted to be located in cytoplasmic vesicle; perinuclear region of cytoplasm; and plasma membrane. Predicted to be active in early endosome membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM184A links:

TMEM184A (HGNC:):

TMEM184A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27763417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM184A	NM_001097620.2 linkuse as main transcript	c.1021G>A	p.Ala341Thr	missense_variant	9/9	ENST00000297477.10	NP_001091089.1	Q6ZMB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM184A	ENST00000297477.10 linkuse as main transcript	c.1021G>A	p.Ala341Thr	missense_variant	9/9	1	NM_001097620.2	ENSP00000297477.4	Q6ZMB5
TMEM184A	ENST00000319018.12 linkuse as main transcript	n.*444G>A		non_coding_transcript_exon_variant	8/8	5		ENSP00000326348.7	F8W8F1
TMEM184A	ENST00000468535.5 linkuse as main transcript	n.1899G>A		non_coding_transcript_exon_variant	6/6	2
TMEM184A	ENST00000319018.12 linkuse as main transcript	n.*444G>A		3_prime_UTR_variant	8/8	5		ENSP00000326348.7	F8W8F1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000623

AC:

AN:

1444826

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

719016

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000815

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2023

The c.1021G>A (p.A341T) alteration is located in exon 9 (coding exon 8) of the TMEM184A gene. This alteration results from a G to A substitution at nucleotide position 1021, causing the alanine (A) at amino acid position 341 to be replaced by a threonine (T). 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

0.078

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

Eigen

Benign

0.080

Eigen_PC

Benign

0.0031

FATHMM_MKL

Benign

0.52

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.73

REVEL

Benign

0.14

Sift

Benign

0.033

Sift4G

Benign

0.21

Polyphen

0.79

Vest4

0.20

MutPred

0.38

Gain of glycosylation at A341 (P = 0.0088);

MVP

0.40

MPC

0.064

ClinPred

0.58

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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