chr4-147617990-C-G

Position:

• chr4-147617990-C-G

Variant summary

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

The NM_018241.3(TMEM184C):​c.34C>G​(p.Gln12Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. 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: 2.28

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

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=0.13727877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM184C	NM_018241.3	c.34C>G	p.Gln12Glu	missense_variant	1/10	ENST00000296582.8	NP_060711.2
TMEM184C	XM_047415958.1	c.34C>G	p.Gln12Glu	missense_variant	1/8		XP_047271914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM184C	ENST00000296582.8	c.34C>G	p.Gln12Glu	missense_variant	1/10	2	NM_018241.3	ENSP00000296582.3
TMEM184C	ENST00000508208.5	c.34C>G	p.Gln12Glu	missense_variant	1/8	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2024

The c.34C>G (p.Q12E) alteration is located in exon 1 (coding exon 1) of the TMEM184C gene. This alteration results from a C to G substitution at nucleotide position 34, causing the glutamine (Q) at amino acid position 12 to be replaced by a glutamic acid (E). 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	0.095
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Benign	0.76
DEOGEN2	Benign	0.032	T;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.74	N;N
REVEL	Benign	0.063
Sift	Benign	0.39	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.049	B;.
Vest4		0.27
MutPred		0.29		Loss of MoRF binding (P = 0.0689);Loss of MoRF binding (P = 0.0689);
MVP		0.076
MPC		0.73
ClinPred		0.40	T
GERP RS		4.6
Varity_R		0.15
gMVP		0.41

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-148539141;