19-48342565-G-C

Position:

• chr19-48342565-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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

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]

TMEM143 (HGNC:):

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=0.09597796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM143	NM_018273.4	c.940C>G	p.Leu314Val	missense_variant	6/8	ENST00000293261.8	NP_060743.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM143	ENST00000293261.8	c.940C>G	p.Leu314Val	missense_variant	6/8	1	NM_018273.4	ENSP00000293261.2
TMEM143	ENST00000377431.6	c.640C>G	p.Leu214Val	missense_variant	4/6	1		ENSP00000366649.1
TMEM143	ENST00000435956.7	c.835C>G	p.Leu279Val	missense_variant	5/7	2		ENSP00000397038.2
TMEM143	ENST00000600816.1	n.427C>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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 20, 2024

The c.940C>G (p.L314V) alteration is located in exon 6 (coding exon 6) of the TMEM143 gene. This alteration results from a C to G substitution at nucleotide position 940, causing the leucine (L) at amino acid position 314 to be replaced by a valine (V). 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	0.081
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.021	T;.;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.86	D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.096	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.50	N;N;N
REVEL	Benign	0.026
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.063	T;T;T
Polyphen		0.0010	B;B;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

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: chr19-48845822;