5-160406482-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006425.5(SLU7):​c.1273A>C​(p.Ile425Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign 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)
• Consequence: SLU7 NM_006425.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.79
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20857802).

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>C	p.Ile425Leu	missense	Exon 12 of 16	NP_006416.3
	SLU7	NM_001364517.2		c.1318A>C	p.Ile440Leu	missense	Exon 12 of 16	NP_001351446.1
	SLU7	NM_001364522.2		c.1303A>C	p.Ile435Leu	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>C	p.Ile425Leu	missense	Exon 12 of 16	ENSP00000297151.4	O95391
	SLU7	ENST00000855629.1		c.1273A>C	p.Ile425Leu	missense	Exon 13 of 17	ENSP00000525688.1
	SLU7	ENST00000938507.1		c.1273A>C	p.Ile425Leu	missense	Exon 12 of 16	ENSP00000608566.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.040	T
Eigen	Benign	0.028
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.8
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.063
Sift	Benign	0.21	T
Sift4G	Benign	0.49	T
Polyphen		0.019	B
Vest4		0.40
MutPred		0.31		Gain of sheet (P = 0.1208)
MVP		0.62
MPC		0.15
ClinPred		0.73	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.46
Mutation Taster		=71/29	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: rs371843592; hg19: chr5-159833489;