Genetic Variant TMEM184A:p.Ser348Ser (chr7-1547150-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001097620.2(TMEM184A):c.1044C>T(p.Ser348Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,607,218 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00069 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

TMEM184A
NM_001097620.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.567

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 made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP7

Synonymous conserved (PhyloP=-0.567 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM184A	NM_001097620.2 link	c.1044C>T	p.Ser348Ser	synonymous_variant	Exon 9 of 9	ENST00000297477.10	NP_001091089.1	Q6ZMB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMEM184A	ENST00000297477.10 link	c.1044C>T	p.Ser348Ser	synonymous_variant	Exon 9 of 9	1	NM_001097620.2	ENSP00000297477.4	Q6ZMB5
TMEM184A	ENST00000319018.12 link	n.*467C>T		non_coding_transcript_exon_variant	Exon 8 of 8	5		ENSP00000326348.7	F8W8F1
TMEM184A	ENST00000468535.5 link	n.1922C>T		non_coding_transcript_exon_variant	Exon 6 of 6	2
TMEM184A	ENST00000319018.12 link	n.*467C>T		3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000326348.7	F8W8F1

Frequencies

GnomAD3 genomes

AF:

0.000690

AC:

105

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000251

AC:

AN:

239438

Hom.:

AF XY:

0.000207

AC XY:

AN XY:

130478

show subpopulations

Gnomad AFR exome

AF:

0.00282

Gnomad AMR exome

AF:

0.000234

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.0000542

Gnomad NFE exome

AF:

0.0000468

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000784

AC:

114

AN:

1455004

Hom.:

Cov.:

AF XY:

0.0000718

AC XY:

AN XY:

723914

show subpopulations

Gnomad4 AFR exome

AF:

0.00224

Gnomad4 AMR exome

AF:

0.000247

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000207

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.000690

AC:

105

AN:

152214

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00246

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000286

Hom.:

Bravo

AF:

0.000820

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.1

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over