5-94643298-G-C

Variant names:

• chr5-94643298-G-C
• rs779510422
• NM_032290.4:c.457G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_032290.4(SLF1):​c.457G>C​(p.Val153Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,540,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: SLF1 NM_032290.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.311
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28681606).

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.457G>C	p.Val153Leu	missense	Exon 5 of 21	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.457G>C	p.Val153Leu	missense	Exon 5 of 21	ENSP00000265140.5	Q9BQI6-1
	SLF1	ENST00000908676.1		c.457G>C	p.Val153Leu	missense	Exon 5 of 21	ENSP00000578735.1
	SLF1	ENST00000966410.1		c.457G>C	p.Val153Leu	missense	Exon 5 of 21	ENSP00000636469.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000134 AC: 2 AN: 149008 AF XY: 0.0000127

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000341

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000133 AC: 184 AN: 1388392 Hom.: 0 Cov.: 29 AF XY: 0.000131 AC XY: 90 AN XY: 684694

African (AFR) AF: 0.0000323 AC: 1 AN: 30920

American (AMR) AF: 0.00 AC: 0 AN: 33038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24844

East Asian (EAS) AF: 0.00 AC: 0 AN: 35372

South Asian (SAS) AF: 0.00 AC: 0 AN: 76986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.000167 AC: 180 AN: 1074722

Other (OTH) AF: 0.0000521 AC: 3 AN: 57630

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152106 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74296

African (AFR) AF: 0.0000241 AC: 1 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000901 Hom.: 0

Bravo AF: 0.0000302

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.31
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.082
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.031	D
Polyphen		0.45	B
Vest4		0.47
MutPred		0.56		Loss of sheet (P = 0.0817)
MVP		0.50
MPC		0.074
ClinPred		0.32	T
GERP RS		1.5
Varity_R		0.14
gMVP		0.47
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs779510422; hg19: chr5-93979003;