5-160403317-C-G

Variant names:

• chr5-160403317-C-G
• rs540085312
• NM_006425.5:c.1729G>C

Variant summary

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

The NM_006425.5(SLU7):​c.1729G>C​(p.Asp577His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,609,762 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D577Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: SLU7 NM_006425.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• 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.

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.1729G>C	p.Asp577His	missense	Exon 16 of 16	NP_006416.3
	SLU7	NM_001364517.2		c.1774G>C	p.Asp592His	missense	Exon 16 of 16	NP_001351446.1
	SLU7	NM_001364522.2		c.1759G>C	p.Asp587His	missense	Exon 16 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.1729G>C	p.Asp577His	missense	Exon 16 of 16	ENSP00000297151.4	O95391
	SLU7	ENST00000855629.1		c.1729G>C	p.Asp577His	missense	Exon 17 of 17	ENSP00000525688.1
	SLU7	ENST00000938507.1		c.1729G>C	p.Asp577His	missense	Exon 16 of 16	ENSP00000608566.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000203 AC: 5 AN: 246844 AF XY: 0.0000225

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000134 AC: 196 AN: 1457466 Hom.: 1 Cov.: 30 AF XY: 0.000112 AC XY: 81 AN XY: 724954

African (AFR) AF: 0.00 AC: 0 AN: 33230

American (AMR) AF: 0.00 AC: 0 AN: 43954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39340

South Asian (SAS) AF: 0.00 AC: 0 AN: 85404

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000175 AC: 194 AN: 1110102

Other (OTH) AF: 0.0000332 AC: 2 AN: 60242

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152296 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74474

African (AFR) AF: 0.0000722 AC: 3 AN: 41558

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000450 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000247 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	Pathogenic	0.68
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.56	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		7.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.99	D
Vest4		0.79
MutPred		0.20		Gain of MoRF binding (P = 0.0321)
MVP		0.76
MPC		0.62
ClinPred		0.82	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.43
Mutation Taster		=34/66	disease causing

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: rs540085312; hg19: chr5-159830324; COSMIC: COSV51787179; COSMIC: COSV51787179;