1-155212373-C-T

Position:

• chr1-155212373-C-T

Variant summary

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

The NM_002455.5(MTX1):​c.772-12C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 1,613,036 control chromosomes in the GnomAD database, including 229,926 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 0.57 (24916 hom., cov: 32)
  • Exomes 𝑓: 0.53 (205010 hom.)
• Consequence: MTX1 NM_002455.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001712
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

Genes affected

MTX1 (HGNC:7504): (metaxin 1) Predicted to be involved in mitochondrion organization. Part of MIB complex and SAM complex. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTX1	NM_002455.5	c.772-12C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000368376.8
MTX1	NM_198883.3	c.679-12C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTX1	ENST00000368376.8	c.772-12C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002455.5
	ENST00000455788.1	n.181-835G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86296 AN: 151944 Hom.: 24877 Cov.: 32

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.556

GnomAD3 exomes AF: 0.565 AC: 141978 AN: 251214 Hom.: 41347 AF XY: 0.553 AC XY: 75146 AN XY: 135782

Gnomad AFR exome AF: 0.654

Gnomad AMR exome AF: 0.687

Gnomad ASJ exome AF: 0.495

Gnomad EAS exome AF: 0.780

Gnomad SAS exome AF: 0.547

Gnomad FIN exome AF: 0.546

Gnomad NFE exome AF: 0.497

Gnomad OTH exome AF: 0.537

GnomAD4 exome AF: 0.525 AC: 767367 AN: 1460974 Hom.: 205010 Cov.: 66 AF XY: 0.523 AC XY: 380045 AN XY: 726650

Gnomad4 AFR exome AF: 0.647

Gnomad4 AMR exome AF: 0.682

Gnomad4 ASJ exome AF: 0.492

Gnomad4 EAS exome AF: 0.808

Gnomad4 SAS exome AF: 0.539

Gnomad4 FIN exome AF: 0.545

Gnomad4 NFE exome AF: 0.504

Gnomad4 OTH exome AF: 0.532

GnomAD4 genome AF: 0.568 AC: 86381 AN: 152062 Hom.: 24916 Cov.: 32 AF XY: 0.570 AC XY: 42342 AN XY: 74320

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.552

Alfa AF: 0.437 Hom.: 2077

Bravo AF: 0.582

Asia WGS AF: 0.664 AC: 2311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.6
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000017
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.040		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: rs2075570; hg19: chr1-155182164;