7-1547142-C-G

Variant names:

• chr7-1547142-C-G
• rs778844659
• NM_001097620.2:c.1052G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001097620.2(TMEM184A):​c.1052G>C​(p.Arg351Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM184A NM_001097620.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.87

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16526192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM184A	NM_001097620.2	c.1052G>C	p.Arg351Thr	missense_variant	Exon 9 of 9	ENST00000297477.10	NP_001091089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM184A	ENST00000297477.10	c.1052G>C	p.Arg351Thr	missense_variant	Exon 9 of 9	1	NM_001097620.2	ENSP00000297477.4
TMEM184A	ENST00000319018.12	n.*475G>C		non_coding_transcript_exon_variant	Exon 8 of 8	5		ENSP00000326348.7
TMEM184A	ENST00000468535.5	n.1930G>C		non_coding_transcript_exon_variant	Exon 6 of 6	2
TMEM184A	ENST00000319018.12	n.*475G>C		3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000326348.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000414 AC: 1 AN: 241524 Hom.: 0 AF XY: 0.00000760 AC XY: 1 AN XY: 131518

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000552

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.047
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.081
Sift	Benign	0.034	D
Sift4G	Benign	0.073	T
Polyphen		0.47	P
Vest4		0.18
MutPred		0.39		Gain of glycosylation at R351 (P = 0.0138);
MVP		0.28
MPC		0.10
ClinPred		0.53	D
GERP RS		1.7
Varity_R		0.27
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

Other links and lift over

dbSNP: rs778844659; hg19: chr7-1586778;