7-1548648-C-T

Variant names:

• chr7-1548648-C-T
• rs149563167
• NM_001097620.2:c.685G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001097620.2(TMEM184A):​c.685G>A​(p.Ala229Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,613,852 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 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. A229S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000046 (1 hom.)
• Consequence: TMEM184A NM_001097620.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.083584726).

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.685G>A	p.Ala229Thr	missense	Exon 7 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.685G>A	p.Ala229Thr	missense	Exon 7 of 9	ENSP00000297477.4	Q6ZMB5
	TMEM184A	ENST00000910337.1		c.700G>A	p.Ala234Thr	missense	Exon 7 of 9	ENSP00000580396.1
	TMEM184A	ENST00000910336.1		c.685G>A	p.Ala229Thr	missense	Exon 7 of 9	ENSP00000580395.1

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152124 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.0000800 AC: 20 AN: 249928 AF XY: 0.0000959

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000710

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000458 AC: 67 AN: 1461610 Hom.: 1 Cov.: 32 AF XY: 0.0000509 AC XY: 37 AN XY: 727126

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26134

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39700

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53204

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1111962

Other (OTH) AF: 0.0000497 AC: 3 AN: 60386

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152242 Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74424

African (AFR) AF: 0.0000482 AC: 2 AN: 41528

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68012

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.0000742 AC: 9

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	17
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.062
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.029
Sift	Benign	0.031	D
Sift4G	Benign	0.074	T
Polyphen		0.015	B
Vest4		0.074
MVP		0.16
MPC		0.062
ClinPred		0.022	T
GERP RS		-4.8
Varity_R		0.062
gMVP		0.72
Mutation Taster		=89/11	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: rs149563167; hg19: chr7-1588284; COSMIC: COSV52472145; COSMIC: COSV52472145;