5-94631044-A-T

Variant names:

• chr5-94631044-A-T
• rs10052066
• NM_032290.4:c.431+301A>T

Variant summary

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

The NM_032290.4(SLF1):​c.431+301A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,984 control chromosomes in the GnomAD database, including 22,486 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 0.54 (22486 hom., cov: 32)
• Consequence: SLF1 NM_032290.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546
• Publications: 9 publications found

Genes affected

SLF1 (HGNC:25408): (SMC5-SMC6 complex localization factor 1) 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 nucleoplasm and site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

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 = 0.61 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032290.4. 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
	SLF1	NM_032290.4	MANE Select	c.431+301A>T		intron	N/A	NP_115666.2	Q9BQI6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLF1	ENST00000265140.10	TSL:2 MANE Select	c.431+301A>T		intron	N/A	ENSP00000265140.5	Q9BQI6-1
	SLF1	ENST00000908676.1		c.431+301A>T		intron	N/A	ENSP00000578735.1
	SLF1	ENST00000966410.1		c.431+301A>T		intron	N/A	ENSP00000636469.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82203 AN: 151866 Hom.: 22463 Cov.: 32

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.541 AC: 82288 AN: 151984 Hom.: 22486 Cov.: 32 AF XY: 0.542 AC XY: 40240 AN XY: 74250

African (AFR) AF: 0.617 AC: 25565 AN: 41464

American (AMR) AF: 0.500 AC: 7641 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1452 AN: 3466

East Asian (EAS) AF: 0.586 AC: 3029 AN: 5168

South Asian (SAS) AF: 0.456 AC: 2196 AN: 4818

European-Finnish (FIN) AF: 0.543 AC: 5713 AN: 10522

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.517 AC: 35097 AN: 67948

Other (OTH) AF: 0.511 AC: 1078 AN: 2108

Alfa AF: 0.424 Hom.: 1249

Bravo AF: 0.541

Asia WGS AF: 0.534 AC: 1853 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.6
DANN	Benign	0.30
PhyloP100		0.55
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: rs10052066; hg19: chr5-93966749;