5-94630530-T-C

Position:

• chr5-94630530-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032290.4(SLF1):​c.218T>C​(p.Ile73Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000214 in 1,399,244 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLF1 NM_032290.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.49

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLF1	NM_032290.4	c.218T>C	p.Ile73Thr	missense_variant	4/21	ENST00000265140.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLF1	ENST00000265140.10	c.218T>C	p.Ile73Thr	missense_variant	4/21	2	NM_032290.4	P1
SLF1	ENST00000504099.5	c.218T>C	p.Ile73Thr	missense_variant	5/5	4
SLF1	ENST00000508130.5	c.218T>C	p.Ile73Thr	missense_variant, NMD_transcript_variant	4/8	2
SLF1	ENST00000466957.1	c.149T>C	p.Ile50Thr	missense_variant, NMD_transcript_variant	3/6	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1399244 Hom.: 0 Cov.: 30 AF XY: 0.00000290 AC XY: 2 AN XY: 690116

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000278

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.40	T
MutationTaster	Benign	0.97	D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.0	N;D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;.
Vest4		0.83
MutPred		0.64		Loss of stability (P = 0.0137);Loss of stability (P = 0.0137);
MVP		0.84
MPC		0.15
ClinPred		0.94	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-93966235;