4-147617970-G-C

Variant names:

• chr4-147617970-G-C
• NM_018241.3:c.14G>C

Variant summary

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

The NM_018241.3(TMEM184C):​c.14G>C​(p.Cys5Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM184C NM_018241.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.65
• Publications: 0 publications found

Genes affected

TMEM184C (HGNC:25587): (transmembrane protein 184C) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM184C	NM_018241.3	c.14G>C	p.Cys5Ser	missense_variant	Exon 1 of 10	ENST00000296582.8	NP_060711.2
TMEM184C	XM_047415958.1	c.14G>C	p.Cys5Ser	missense_variant	Exon 1 of 8		XP_047271914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM184C	ENST00000296582.8	c.14G>C	p.Cys5Ser	missense_variant	Exon 1 of 10	2	NM_018241.3	ENSP00000296582.3
TMEM184C	ENST00000508208.5	c.14G>C	p.Cys5Ser	missense_variant	Exon 1 of 8	1		ENSP00000425940.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.14G>C (p.C5S) alteration is located in exon 1 (coding exon 1) of the TMEM184C gene. This alteration results from a G to C substitution at nucleotide position 14, causing the cysteine (C) at amino acid position 5 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.065	T;T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.1	M;.
PhyloP100		5.7
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.19
Sift	Uncertain	0.023	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		0.038	B;.
Vest4		0.68
MutPred		0.47		Gain of disorder (P = 2e-04);Gain of disorder (P = 2e-04);
MVP		0.21
MPC		0.90
ClinPred		0.82	D
GERP RS		5.5
Varity_R		0.38
gMVP		0.58
Mutation Taster		=38/62	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

hg19: chr4-148539121;