chr4-147623927-C-A

Position:

• chr4-147623927-C-A

Variant summary

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

The NM_018241.3(TMEM184C):​c.217C>A​(p.His73Asn) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 7.91

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM184C	NM_018241.3	c.217C>A	p.His73Asn	missense_variant	2/10	ENST00000296582.8	NP_060711.2
TMEM184C	XM_047415958.1	c.217C>A	p.His73Asn	missense_variant	2/8		XP_047271914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM184C	ENST00000296582.8	c.217C>A	p.His73Asn	missense_variant	2/10	2	NM_018241.3	ENSP00000296582.3
TMEM184C	ENST00000508208.5	c.217C>A	p.His73Asn	missense_variant	2/8	1		ENSP00000425940.1

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 23, 2024

The c.217C>A (p.H73N) alteration is located in exon 2 (coding exon 2) of the TMEM184C gene. This alteration results from a C to A substitution at nucleotide position 217, causing the histidine (H) at amino acid position 73 to be replaced by an asparagine (N). 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	0.21
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.17	T;T
Eigen	Benign	-0.096
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.66	N;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.8	D;D
REVEL	Benign	0.22
Sift	Benign	0.14	T;T
Sift4G	Benign	0.64	T;T
Polyphen		0.046	B;.
Vest4		0.73
MutPred		0.49		Loss of disorder (P = 0.1456);Loss of disorder (P = 0.1456);
MVP		0.25
MPC		0.81
ClinPred		0.67	D
GERP RS		5.4
Varity_R		0.55
gMVP		0.86

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: chr4-148545078;