10-100932847-T-C

Variant names:

• chr10-100932847-T-C
• rs12241232
• NM_018121.4:c.2436+1769T>C

Variant summary

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

The NM_018121.4(SLF2):​c.2436+1769T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 149,050 control chromosomes in the GnomAD database, including 5,870 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 0.27 (5870 hom., cov: 31)
• Consequence: SLF2 NM_018121.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 8 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLF2	NM_018121.4	c.2436+1769T>C		intron_variant	Intron 9 of 19	ENST00000238961.9	NP_060591.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLF2	ENST00000238961.9	c.2436+1769T>C		intron_variant	Intron 9 of 19	1	NM_018121.4	ENSP00000238961.3
SLF2	ENST00000370269.3	c.2436+1769T>C		intron_variant	Intron 9 of 18	1		ENSP00000359292.3
SLF2	ENST00000649226.1	n.*467+1769T>C		intron_variant	Intron 10 of 20			ENSP00000496951.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 39509 AN: 148928 Hom.: 5861 Cov.: 31

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.179

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.265 AC: 39551 AN: 149050 Hom.: 5870 Cov.: 31 AF XY: 0.269 AC XY: 19520 AN XY: 72618

African (AFR) AF: 0.348 AC: 14332 AN: 41196

American (AMR) AF: 0.299 AC: 4376 AN: 14628

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 498 AN: 3436

East Asian (EAS) AF: 0.563 AC: 2897 AN: 5144

South Asian (SAS) AF: 0.354 AC: 1629 AN: 4596

European-Finnish (FIN) AF: 0.180 AC: 1813 AN: 10052

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.199 AC: 13305 AN: 66790

Other (OTH) AF: 0.253 AC: 516 AN: 2042

Alfa AF: 0.227 Hom.: 750

Bravo AF: 0.276

Asia WGS AF: 0.437 AC: 1519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.0
DANN	Benign	0.49
PhyloP100		0.13
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: rs12241232; hg19: chr10-102692604;