ENST00000456633.3:n.4228G>A

Variant names:

• chr1-155566947-G-A
• rs8179271
• ENST00000456633.3:n.4228G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000456633.3(ASH1L-AS1):​n.4228G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0594 in 152,030 control chromosomes in the GnomAD database, including 1,555 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 0.059 (1555 hom., cov: 31)
• Consequence: ASH1L-AS1 ENST00000456633.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320
• Publications: 8 publications found

Genes affected

ASH1L-AS1 (HGNC:44146): (ASH1L antisense RNA 1)

MSTO1 (HGNC:29678): (misato mitochondrial distribution and morphology regulator 1) Involved in mitochondrion distribution. Located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

MSTO1 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Broad Center for Mendelian Genomics, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSTO1	XM_047424007.1	c.-608+3618G>A		intron_variant	Intron 1 of 17		XP_047279963.1
MSTO1	XM_047424008.1	c.-524+3618G>A		intron_variant	Intron 1 of 16		XP_047279964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASH1L-AS1	ENST00000456633.3	n.4228G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
MSTO1	ENST00000697770.1	c.-379+3618G>A		intron_variant	Intron 1 of 12			ENSP00000513434.1

Frequencies

GnomAD3 genomes AF: 0.0593 AC: 9010 AN: 151912 Hom.: 1549 Cov.: 31

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.0626

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0576

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

GnomAD4 genome AF: 0.0594 AC: 9023 AN: 152030 Hom.: 1555 Cov.: 31 AF XY: 0.0683 AC XY: 5076 AN XY: 74298

African (AFR) AF: 0.0133 AC: 553 AN: 41518

American (AMR) AF: 0.143 AC: 2189 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3468

East Asian (EAS) AF: 0.676 AC: 3465 AN: 5126

South Asian (SAS) AF: 0.198 AC: 955 AN: 4812

European-Finnish (FIN) AF: 0.0626 AC: 662 AN: 10570

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0135 AC: 920 AN: 67968

Other (OTH) AF: 0.0556 AC: 117 AN: 2106

Alfa AF: 0.0389 Hom.: 1613

Bravo AF: 0.0699

Asia WGS AF: 0.403 AC: 1398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.42
PhyloP100		0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8179271; hg19: chr1-155536738;