chr5-94628821-G-A

Variant names:

• chr5-94628821-G-A
• rs199976521
• NM_032290.4:c.11G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032290.4(SLF1):​c.11G>A​(p.Gly4Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000872 in 1,536,962 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 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000092 (0 hom.)
• Consequence: SLF1 NM_032290.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.289
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048959523).

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.11G>A	p.Gly4Asp	missense	Exon 2 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.11G>A	p.Gly4Asp	missense	Exon 2 of 21	ENSP00000265140.5	Q9BQI6-1
	SLF1	ENST00000908676.1		c.11G>A	p.Gly4Asp	missense	Exon 2 of 21	ENSP00000578735.1
	SLF1	ENST00000966410.1		c.11G>A	p.Gly4Asp	missense	Exon 2 of 21	ENSP00000636469.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152072 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000945

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000668 AC: 10 AN: 149704 AF XY: 0.0000890

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: 0.0000592

Gnomad NFE exome AF: 0.000152

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000917 AC: 127 AN: 1384890 Hom.: 0 Cov.: 29 AF XY: 0.0000747 AC XY: 51 AN XY: 682426

African (AFR) AF: 0.0000324 AC: 1 AN: 30902

American (AMR) AF: 0.00 AC: 0 AN: 32956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24690

East Asian (EAS) AF: 0.00 AC: 0 AN: 35480

South Asian (SAS) AF: 0.00 AC: 0 AN: 75832

European-Finnish (FIN) AF: 0.000162 AC: 8 AN: 49300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 0.000104 AC: 112 AN: 1072586

Other (OTH) AF: 0.000104 AC: 6 AN: 57520

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152072 Hom.: 0 Cov.: 33 AF XY: 0.0000539 AC XY: 4 AN XY: 74264

African (AFR) AF: 0.00 AC: 0 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

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

European-Finnish (FIN) AF: 0.0000945 AC: 1 AN: 10580

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000854 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.000119 AC: 3

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	0.065
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	9.8
DANN	Benign	0.34
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.99	T
PhyloP100		-0.29
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.10
Sift	Benign	0.16	T
Sift4G	Benign	0.48	T
Polyphen		0.0020	B
Vest4		0.11
MutPred		0.15		Gain of loop (P = 0.069)
MVP		0.42
MPC		0.088
ClinPred		0.024	T
GERP RS		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.052
gMVP		0.23
Mutation Taster		=98/2	polymorphism

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: rs199976521; hg19: chr5-93964526;