Genetic Variant TMEM184A:p.Pro285Leu (chr7-1547900-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001097620.2(TMEM184A):c.854C>T(p.Pro285Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,592,340 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.00019 ( 2 hom. )

Consequence

TMEM184A
NM_001097620.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.66

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.898

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001097620.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM184A	NM_001097620.2	MANE Select	c.854C>T	p.Pro285Leu	missense	Exon 8 of 9	NP_001091089.1	Q6ZMB5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM184A	ENST00000297477.10	TSL:1 MANE Select	c.854C>T	p.Pro285Leu	missense	Exon 8 of 9	ENSP00000297477.4	Q6ZMB5
TMEM184A	ENST00000910337.1		c.869C>T	p.Pro290Leu	missense	Exon 8 of 9	ENSP00000580396.1
TMEM184A	ENST00000910336.1		c.854C>T	p.Pro285Leu	missense	Exon 8 of 9	ENSP00000580395.1

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

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:

0.000162

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000530

AC:

AN:

207440

AF XY:

0.0000619

show subpopulations

Gnomad AFR exome

AF:

0.0000856

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000995

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000190

AC:

273

AN:

1440174

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

112

AN XY:

714694

show subpopulations

African (AFR)

AF:

0.0000607

AC:

AN:

32958

American (AMR)

AF:

0.00

AC:

AN:

42002

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25704

East Asian (EAS)

AF:

0.00

AC:

AN:

38336

South Asian (SAS)

AF:

0.0000240

AC:

AN:

83320

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5586

European-Non Finnish (NFE)

AF:

0.000238

AC:

262

AN:

1102212

Other (OTH)

AF:

0.000118

AC:

AN:

59550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0000966

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000112

Hom.:

Bravo

AF:

0.0000793

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000475

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.0000585

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.043

MetaRNN

Pathogenic

0.90

MetaSVM

Benign

-0.42

MutationAssessor

Pathogenic

2.9

PhyloP100

9.7

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.48

Sift

Uncertain

0.010

Sift4G

Uncertain

0.017

Polyphen

0.99

Vest4

0.95

MVP

0.51

MPC

0.35

ClinPred

0.91

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

gMVP

0.90

Mutation Taster

=26/74

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over