3-129158157-C-G

Variant names:

• chr3-129158157-C-G
• rs2342286
• NM_020701.4:c.78+351G>C

Variant summary

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

The NM_020701.4(ISY1):​c.78+351G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0776 in 141,152 control chromosomes in the GnomAD database, including 1,351 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 0.078 (1351 hom., cov: 28)
• Consequence: ISY1 NM_020701.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 0 publications found

Genes affected

ISY1 (HGNC:29201): (ISY1 splicing factor homolog) Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nucleus. Part of U2-type catalytic step 1 spliceosome and catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

ISY1-RAB43 (HGNC:42969): (ISY1-RAB43 readthrough) This locus represents naturally occurring read-through transcription between the neighboring ISY1 (ISY1 splicing factor homolog) and RAB43 (RAB43, member RAS oncogene family) gene on chromosome 3. The read-through transcript encodes a protein that shares sequence identity with the upstream gene product, but its C-terminus is distinct due to a frameshift relative to the downstream gene. [provided by RefSeq, Mar 2011]

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 (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020701.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ISY1	NM_020701.4	MANE Select	c.78+351G>C		intron	N/A	NP_065752.1	Q9ULR0-3
	ISY1-RAB43	NM_001204890.2		c.78+351G>C		intron	N/A	NP_001191819.1
	ISY1	NM_001199469.2		c.78+351G>C		intron	N/A	NP_001186398.1	Q9ULR0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ISY1	ENST00000393295.8	TSL:1 MANE Select	c.78+351G>C		intron	N/A	ENSP00000376973.4	Q9ULR0-3
	ISY1-RAB43	ENST00000418265.1	TSL:2	c.78+351G>C		intron	N/A	ENSP00000411822.1
	ISY1	ENST00000273541.12	TSL:1	c.78+351G>C		intron	N/A	ENSP00000273541.8	Q9ULR0-2

Frequencies

GnomAD3 genomes AF: 0.0775 AC: 10944 AN: 141136 Hom.: 1347 Cov.: 28

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.00669

Gnomad EAS AF: 0.000204

Gnomad SAS AF: 0.00136

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0364

Gnomad NFE AF: 0.00127

Gnomad OTH AF: 0.0616

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

GnomAD4 genome AF: 0.0776 AC: 10952 AN: 141152 Hom.: 1351 Cov.: 28 AF XY: 0.0741 AC XY: 5072 AN XY: 68488

African (AFR) AF: 0.261 AC: 10187 AN: 39086

American (AMR) AF: 0.0379 AC: 531 AN: 14026

Ashkenazi Jewish (ASJ) AF: 0.00669 AC: 22 AN: 3288

East Asian (EAS) AF: 0.000205 AC: 1 AN: 4880

South Asian (SAS) AF: 0.00114 AC: 5 AN: 4392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8530

Middle Eastern (MID) AF: 0.0290 AC: 8 AN: 276

European-Non Finnish (NFE) AF: 0.00127 AC: 81 AN: 63888

Other (OTH) AF: 0.0613 AC: 117 AN: 1908

Alfa AF: 0.00213 Hom.: 2

Bravo AF: 0.0859

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.49
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2342286; hg19: chr3-128877000;