15-79900633-C-T

Variant summary

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

The NM_001199760.2(ST20-MTHFS):c.45+6996G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0495 in 152,090 control chromosomes in the GnomAD database, including 494 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 0.050 (494 hom., cov: 33)
• Consequence: ST20-MTHFS NM_001199760.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.664

Genes affected

ST20-MTHFS (HGNC:):

ST20 (HGNC:33520): (suppressor of tumorigenicity 20) Enables cysteine-type endopeptidase activator activity involved in apoptotic process. Involved in several processes, including apoptotic signaling pathway; cellular response to UV-C; and positive regulation of nitrogen compound metabolic process. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST20-MTHFS	NM_001199760.2	c.45+6996G>A		intron_variant
ST20	NR_037652.2	n.358-1508G>A		intron_variant, non_coding_transcript_variant
ST20	NR_037653.2	n.380-1508G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST20	ENST00000478497.5	n.726-1508G>A		intron_variant, non_coding_transcript_variant		1
ST20	ENST00000485386.1	n.308-1508G>A		intron_variant, non_coding_transcript_variant		1
ST20	ENST00000562759.1	n.409-1508G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0496 AC: 7536 AN: 151972 Hom.: 494 Cov.: 33

Gnomad AFR AF: 0.00892

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0412

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

GnomAD4 genome AF: 0.0495 AC: 7533 AN: 152090 Hom.: 494 Cov.: 33 AF XY: 0.0554 AC XY: 4117 AN XY: 74322

Gnomad4 AFR AF: 0.00889

Gnomad4 AMR AF: 0.0173

Gnomad4 ASJ AF: 0.0389

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.0462

Gnomad4 OTH AF: 0.0408

Alfa AF: 0.0491 Hom.: 40

Bravo AF: 0.0381

Asia WGS AF: 0.190 AC: 655 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.7
Dann	Benign	0.65

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: rs36035742; hg19: chr15-80192975;