chr5-160419067-A-G

Variant names:

• chr5-160419067-A-G
• rs17057781
• NM_006425.5:c.-61T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006425.5(SLU7):​c.-61T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,284 control chromosomes in the GnomAD database, including 1,585 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1584 hom., cov: 32)
  • Exomes 𝑓: 0.17 (1 hom.)
• Consequence: SLU7 NM_006425.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• Publications: 17 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLU7	NM_006425.5	MANE Select	c.-61T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	NP_006416.3
	SLU7	NM_006425.5	MANE Select	c.-61T>C		5_prime_UTR	Exon 1 of 16	NP_006416.3
	SLU7	NM_001364517.2		c.-14T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	NP_001351446.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLU7	ENST00000297151.9	TSL:1 MANE Select	c.-61T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	ENSP00000297151.4
	SLU7	ENST00000520664.1	TSL:1	c.-488T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000428362.1
	SLU7	ENST00000297151.9	TSL:1 MANE Select	c.-61T>C		5_prime_UTR	Exon 1 of 16	ENSP00000297151.4

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21569 AN: 152136 Hom.: 1584 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.167 AC: 5 AN: 30 Hom.: 1 Cov.: 0 AF XY: 0.150 AC XY: 3 AN XY: 20

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 4 AN: 24

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.142 AC: 21579 AN: 152254 Hom.: 1584 Cov.: 32 AF XY: 0.142 AC XY: 10538 AN XY: 74436

African (AFR) AF: 0.126 AC: 5234 AN: 41552

American (AMR) AF: 0.102 AC: 1568 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 562 AN: 3470

East Asian (EAS) AF: 0.206 AC: 1064 AN: 5174

South Asian (SAS) AF: 0.199 AC: 959 AN: 4824

European-Finnish (FIN) AF: 0.154 AC: 1627 AN: 10588

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9952 AN: 68016

Other (OTH) AF: 0.157 AC: 332 AN: 2116

Alfa AF: 0.145 Hom.: 2137

Bravo AF: 0.137

Asia WGS AF: 0.207 AC: 721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.0
DANN	Benign	0.42
PhyloP100		0.14
PromoterAI		0.14	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs17057781; hg19: chr5-159846074;