19-48342567-A-C

Variant summary

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

The NM_018273.4(TMEM143):c.938T>G(p.Leu313Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,218 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TMEM143 NM_018273.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13

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

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	UniProt
TMEM143	NM_018273.4	c.938T>G	p.Leu313Arg	missense_variant	6/8	ENST00000293261.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM143	ENST00000293261.8	c.938T>G	p.Leu313Arg	missense_variant	6/8	1	NM_018273.4	P1
TMEM143	ENST00000377431.6	c.638T>G	p.Leu213Arg	missense_variant	4/6	1
TMEM143	ENST00000435956.7	c.833T>G	p.Leu278Arg	missense_variant	5/7	2
TMEM143	ENST00000600816.1	n.425T>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460218 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 726444

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

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

Feb 13, 2024

The c.938T>G (p.L313R) alteration is located in exon 6 (coding exon 6) of the TMEM143 gene. This alteration results from a T to G substitution at nucleotide position 938, causing the leucine (L) at amino acid position 313 to be replaced by an arginine (R). 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	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.;T
Eigen	Benign	0.094
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.8	L;.;.
MutationTaster	Benign	0.81	N;N;N;N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.28
Sift	Benign	0.031	D;T;T
Sift4G	Benign	0.065	T;T;T
Polyphen		0.26	B;D;B
Vest4		0.85
MutPred		0.72		Gain of methylation at L313 (P = 0.0073);.;.;
MVP		0.54
MPC		0.36
ClinPred		0.74	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.77

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: chr19-48845824;