chr4-147634291-C-T

Position:

• chr4-147634291-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018241.3(TMEM184C):​c.1174C>T​(p.Pro392Ser) 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. 15/20 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: 0.196

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.023104489).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM184C	NM_018241.3	c.1174C>T	p.Pro392Ser	missense_variant	10/10	ENST00000296582.8	NP_060711.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM184C	ENST00000296582.8	c.1174C>T	p.Pro392Ser	missense_variant	10/10	2	NM_018241.3	ENSP00000296582.3
TMEM184C	ENST00000508208.5	c.779+2786C>T		intron_variant		1		ENSP00000425940.1
TMEM184C	ENST00000505999.5	n.*318C>T		non_coding_transcript_exon_variant	5/5	5		ENSP00000421159.1
TMEM184C	ENST00000505999.5	n.*318C>T		3_prime_UTR_variant	5/5	5		ENSP00000421159.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Apr 25, 2023

The c.1174C>T (p.P392S) alteration is located in exon 10 (coding exon 10) of the TMEM184C gene. This alteration results from a C to T substitution at nucleotide position 1174, causing the proline (P) at amino acid position 392 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	0.062
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.86
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.38	N
MutationTaster	Benign	0.93	D;D
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.055
Sift	Benign	0.43	T
Sift4G	Benign	0.96	T
Polyphen		0.0010	B
Vest4		0.071
MutPred		0.23		Gain of relative solvent accessibility (P = 0.0023);
MVP		0.048
MPC		0.68
ClinPred		0.089	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.020
gMVP		0.35

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

LitVar

Other links and lift over

dbSNP: rs1560955942; hg19: chr4-148555442;