Genetic Variant TMEM184A:p.Lys333Arg (chr7-1547756-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001097620.2(TMEM184A):c.998A>G(p.Lys333Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,460,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TMEM184A
NM_001097620.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96

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:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05072832).

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.998A>G	p.Lys333Arg	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.998A>G	p.Lys333Arg	missense	Exon 8 of 9	ENSP00000297477.4	Q6ZMB5
TMEM184A	ENST00000910337.1		c.1013A>G	p.Lys338Arg	missense	Exon 8 of 9	ENSP00000580396.1
TMEM184A	ENST00000910336.1		c.998A>G	p.Lys333Arg	missense	Exon 8 of 9	ENSP00000580395.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000244

AC:

AN:

246180

AF XY:

0.0000224

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000335

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460140

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44650

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.000126

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86008

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52468

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111676

Other (OTH)

AF:

0.0000166

AC:

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000331

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

0.072

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.0091

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.67

M_CAP

Benign

0.024

MetaRNN

Benign

0.051

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

4.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.51

REVEL

Benign

0.13

Sift

Benign

0.51

Sift4G

Benign

0.45

Polyphen

0.0010

Vest4

0.28

MutPred

0.36

Loss of methylation at K333 (P = 0.0038)

MVP

0.16

MPC

0.052

ClinPred

0.037

GERP RS

0.64

Varity_R

0.036

gMVP

0.60

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over