NM_018273.4:c.940C>G

Variant names:

• chr19-48342565-G-C
• NM_018273.4:c.940C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018273.4(TMEM143):​c.940C>G​(p.Leu314Val) 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. 16/22 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: TMEM143 NM_018273.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0820
• Publications: 0 publications found

Genes affected

TMEM143 (HGNC:25603): (transmembrane protein 143) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09597796).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018273.4. 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
	TMEM143	NM_018273.4	MANE Select	c.940C>G	p.Leu314Val	missense	Exon 6 of 8	NP_060743.2
	TMEM143	NM_001303538.2		c.835C>G	p.Leu279Val	missense	Exon 5 of 7	NP_001290467.1	B4DMT0
	TMEM143	NM_001303539.2		c.745C>G	p.Leu249Val	missense	Exon 5 of 7	NP_001290468.1	B4DPF8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM143	ENST00000293261.8	TSL:1 MANE Select	c.940C>G	p.Leu314Val	missense	Exon 6 of 8	ENSP00000293261.2	Q96AN5-1
	TMEM143	ENST00000377431.6	TSL:1	c.640C>G	p.Leu214Val	missense	Exon 4 of 6	ENSP00000366649.1	Q96AN5-2
	TMEM143	ENST00000948722.1		c.937C>G	p.Leu313Val	missense	Exon 6 of 8	ENSP00000618781.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.082
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.026
Sift	Benign	0.31	T
Sift4G	Benign	0.063	T
Polyphen		0.0010	B
Vest4		0.38
MutPred		0.44		Gain of MoRF binding (P = 0.0941)
MVP		0.26
MPC		0.24
ClinPred		0.12	T
GERP RS		-1.3
Varity_R		0.11
gMVP		0.43
Mutation Taster		=94/6	polymorphism

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: chr19-48845822;