chr5-160406482-T-A

Variant names:

• chr5-160406482-T-A
• rs371843592
• NM_006425.5:c.1273A>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006425.5(SLU7):​c.1273A>T​(p.Ile425Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I425N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLU7 NM_006425.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.79
• Publications: 0 publications found

Genes affected

SLU7 (HGNC:16939): (SLU7 homolog, splicing factor) Pre-mRNA splicing occurs in two sequential transesterification steps. The protein encoded by this gene is a splicing factor that has been found to be essential during the second catalytic step in the pre-mRNA splicing process. It associates with the spliceosome and contains a zinc knuckle motif that is found in other splicing factors and is involved in protein-nucleic acid and protein-protein interactions. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.763

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006425.5. 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
	SLU7	NM_006425.5	MANE Select	c.1273A>T	p.Ile425Phe	missense	Exon 12 of 16	NP_006416.3
	SLU7	NM_001364517.2		c.1318A>T	p.Ile440Phe	missense	Exon 12 of 16	NP_001351446.1
	SLU7	NM_001364522.2		c.1303A>T	p.Ile435Phe	missense	Exon 12 of 16	NP_001351451.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLU7	ENST00000297151.9	TSL:1 MANE Select	c.1273A>T	p.Ile425Phe	missense	Exon 12 of 16	ENSP00000297151.4	O95391
	SLU7	ENST00000855629.1		c.1273A>T	p.Ile425Phe	missense	Exon 13 of 17	ENSP00000525688.1
	SLU7	ENST00000938507.1		c.1273A>T	p.Ile425Phe	missense	Exon 12 of 16	ENSP00000608566.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457156 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724964

African (AFR) AF: 0.00 AC: 0 AN: 33036

American (AMR) AF: 0.00 AC: 0 AN: 43418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25966

East Asian (EAS) AF: 0.00 AC: 0 AN: 39364

South Asian (SAS) AF: 0.00 AC: 0 AN: 85586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110486

Other (OTH) AF: 0.0000166 AC: 1 AN: 60186

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.54	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		5.8
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.22
Sift	Uncertain	0.020	D
Sift4G	Benign	0.12	T
Polyphen		0.96	D
Vest4		0.81
MutPred		0.34		Gain of ubiquitination at K424 (P = 0.1062)
MVP		0.74
MPC		0.67
ClinPred		0.97	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.66
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs371843592; hg19: chr5-159833489;