rs275838

chr19-48362957-C-Achr19-48362957-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018273.4(TMEM143):c.264+334G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,052 control chromosomes in the GnomAD database, including 38,017 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.70 (38017 hom., cov: 33)
• Consequence: TMEM143 NM_018273.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM143	NM_018273.4	c.264+334G>T		intron_variant		ENST00000293261.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM143	ENST00000293261.8	c.264+334G>T		intron_variant		1	NM_018273.4	P1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106471 AN: 151932 Hom.: 37990 Cov.: 33

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.735

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.701 AC: 106544 AN: 152052 Hom.: 38017 Cov.: 33 AF XY: 0.702 AC XY: 52158 AN XY: 74318

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.793

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.738

Alfa AF: 0.740 Hom.: 41380

Bravo AF: 0.701

Asia WGS AF: 0.775 AC: 2693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.4
Dann	Benign	0.58

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: rs275838; hg19: chr19-48866214;