chr10-100919331-T-A

Variant names:

• chr10-100919331-T-A
• rs1969724
• NM_018121.4:c.973+890T>A

Variant summary

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

The NM_018121.4(SLF2):​c.973+890T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 152,044 control chromosomes in the GnomAD database, including 52,626 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 0.83 (52626 hom., cov: 30)
• Consequence: SLF2 NM_018121.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425
• Publications: 0 publications found

Genes affected

SLF2 (HGNC:17814): (SMC5-SMC6 complex localization factor 2) Enables ubiquitin protein ligase binding activity. Involved in several processes, including positive regulation of cellular component organization; positive regulation of double-strand break repair; and protein localization to site of double-strand break. Located in chromatin; nucleoplasm; and site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

SLF2 Gene-Disease associations (from GenCC):

• Atelis syndrome 1

  Inheritance: AR Classification: MODERATE Submitted by: G2P, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018121.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLF2	NM_018121.4	MANE Select	c.973+890T>A		intron	N/A	NP_060591.3
	SLF2	NM_001136123.2		c.973+890T>A		intron	N/A	NP_001129595.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLF2	ENST00000238961.9	TSL:1 MANE Select	c.973+890T>A		intron	N/A	ENSP00000238961.3
	SLF2	ENST00000370269.3	TSL:1	c.973+890T>A		intron	N/A	ENSP00000359292.3
	SLF2	ENST00000370271.7	TSL:1	c.973+890T>A		intron	N/A	ENSP00000359294.3

Frequencies

GnomAD3 genomes AF: 0.830 AC: 126169 AN: 151926 Hom.: 52580 Cov.: 30

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.838

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

GnomAD4 genome AF: 0.831 AC: 126274 AN: 152044 Hom.: 52626 Cov.: 30 AF XY: 0.828 AC XY: 61562 AN XY: 74322

African (AFR) AF: 0.862 AC: 35750 AN: 41464

American (AMR) AF: 0.848 AC: 12950 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2784 AN: 3472

East Asian (EAS) AF: 0.658 AC: 3391 AN: 5152

South Asian (SAS) AF: 0.783 AC: 3779 AN: 4826

European-Finnish (FIN) AF: 0.811 AC: 8556 AN: 10548

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.829 AC: 56346 AN: 67990

Other (OTH) AF: 0.835 AC: 1764 AN: 2112

Alfa AF: 0.827 Hom.: 6482

Bravo AF: 0.836

Asia WGS AF: 0.712 AC: 2479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.1
DANN	Benign	0.76
PhyloP100		0.42
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: rs1969724; hg19: chr10-102679088;