5-94695113-G-T

Position:

• chr5-94695113-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032290.4(SLF1):​c.2978G>T​(p.Cys993Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLF1 NM_032290.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016307831).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLF1	NM_032290.4	c.2978G>T	p.Cys993Phe	missense_variant	21/21	ENST00000265140.10	NP_115666.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLF1	ENST00000265140.10	c.2978G>T	p.Cys993Phe	missense_variant	21/21	2	NM_032290.4	ENSP00000265140	P1
SLF1	ENST00000450932.2	n.1560G>T		non_coding_transcript_exon_variant	7/7	1
SLF1	ENST00000493934.1	n.71+2857G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2 AN: 151604 Hom.: 0 Cov.: 32 FAILED QC

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000296

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00708 AC: 10110 AN: 1428408 Hom.: 0 Cov.: 31 AF XY: 0.00803 AC XY: 5681 AN XY: 707644

Gnomad4 AFR exome AF: 0.0122

Gnomad4 AMR exome AF: 0.0588

Gnomad4 ASJ exome AF: 0.0185

Gnomad4 EAS exome AF: 0.0278

Gnomad4 SAS exome AF: 0.0120

Gnomad4 FIN exome AF: 0.0214

Gnomad4 NFE exome AF: 0.00315

Gnomad4 OTH exome AF: 0.00538

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000264 AC: 4 AN: 151712 Hom.: 0 Cov.: 32 AF XY: 0.0000540 AC XY: 4 AN XY: 74140

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000296

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00109 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.105 AC: 12701

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	11
DANN	Benign	0.96
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.10
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.026	D
Polyphen		0.068	B
Vest4		0.10
MPC		0.11
ClinPred		0.0010	T
GERP RS		2.6
Varity_R		0.24
gMVP		0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs76504036; hg19: chr5-94030818; COSMIC: COSV54367577; COSMIC: COSV54367577;