Variant chr7-1546969-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000297477.10(TMEM184A):c.1225C>T(p.Pro409Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,588,902 control chromosomes in the GnomAD database, including 2 homozygotes. 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. P409A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 2 hom. )

Consequence

TMEM184A
ENST00000297477.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.861

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05017215).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM184A	NM_001097620.2 linkuse as main transcript	c.1225C>T	p.Pro409Ser	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.1225C>T	p.Pro409Ser	missense_variant	9/9	1	NM_001097620.2	ENSP00000297477.4	Q6ZMB5
TMEM184A	ENST00000319018.12 linkuse as main transcript	n.*648C>T		non_coding_transcript_exon_variant	8/8	5		ENSP00000326348.7	F8W8F1
TMEM184A	ENST00000468535.5 linkuse as main transcript	n.2103C>T		non_coding_transcript_exon_variant	6/6	2
TMEM184A	ENST00000319018.12 linkuse as main transcript	n.*648C>T		3_prime_UTR_variant	8/8	5		ENSP00000326348.7	F8W8F1

Frequencies

GnomAD3 genomes

AF:

0.0000987

AC:

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000707

AC:

AN:

212190

Hom.:

AF XY:

0.0000680

AC XY:

AN XY:

117726

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000159

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000160

AC:

230

AN:

1436896

Hom.:

Cov.:

AF XY:

0.000146

AC XY:

104

AN XY:

714582

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:

0.000199

Gnomad4 OTH exome

AF:

0.000168

GnomAD4 genome

AF:

0.0000987

AC:

AN:

152006

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000106

ExAC

AF:

0.0000168

AC:

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

Jun 21, 2022

The c.1225C>T (p.P409S) alteration is located in exon 9 (coding exon 8) of the TMEM184A gene. This alteration results from a C to T substitution at nucleotide position 1225, causing the proline (P) at amino acid position 409 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

0.083

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.7

DANN

Benign

0.62

DEOGEN2

Benign

0.0023

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.77

M_CAP

Benign

0.021

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

0.88

PrimateAI

Benign

0.41

PROVEAN

Benign

0.30

REVEL

Benign

0.059

Sift

Benign

0.71

Sift4G

Benign

0.82

Polyphen

0.0010

Vest4

0.036

MVP

0.22

MPC

0.061

ClinPred

0.056

GERP RS

5.4

Varity_R

0.066

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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