7-1547058-G-T

Variant names:

• chr7-1547058-G-T
• rs376429579
• NM_001097620.2:c.1136C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001097620.2(TMEM184A):​c.1136C>A​(p.Thr379Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,456,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T379M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TMEM184A NM_001097620.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1467123).

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.1136C>A	p.Thr379Lys	missense	Exon 9 of 9	NP_001091089.1	Q6ZMB5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM184A	ENST00000297477.10	TSL:1 MANE Select	c.1136C>A	p.Thr379Lys	missense	Exon 9 of 9	ENSP00000297477.4	Q6ZMB5
	TMEM184A	ENST00000910337.1		c.1151C>A	p.Thr384Lys	missense	Exon 9 of 9	ENSP00000580396.1
	TMEM184A	ENST00000910336.1		c.1136C>A	p.Thr379Lys	missense	Exon 9 of 9	ENSP00000580395.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456774 Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1 AN XY: 724874

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86184

European-Finnish (FIN) AF: 0.0000202 AC: 1 AN: 49522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5340

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111560

Other (OTH) AF: 0.00 AC: 0 AN: 60282

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.0099	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.1
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.12
Sift	Benign	0.34	T
Sift4G	Benign	0.60	T
Polyphen		0.79	P
Vest4		0.18
MutPred		0.31		Gain of ubiquitination at T379 (P = 0.0029)
MVP		0.32
MPC		0.13
ClinPred		0.44	T
GERP RS		2.1
Varity_R		0.071
gMVP		0.70
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs376429579; hg19: chr7-1586694;