rs317608

Positions:

• chr3-4034252-G-A
• chr3-4034252-G-C
• chr3-4034252-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000661097.1(ENSG00000287720):​n.450+4127G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,120 control chromosomes in the GnomAD database, including 59,322 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 0.88 (59322 hom., cov: 32)
• Consequence: ENST00000661097.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.439

Genes affected

(HGNC:):

SUMF1 (HGNC:20376): (sulfatase modifying factor 1) This gene encodes an enzyme that catalyzes the hydrolysis of sulfate esters by oxidizing a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue, which is also known as C-alpha-formylglycine. Mutations in this gene cause multiple sulfatase deficiency, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC102723512	XR_007095788.1	n.1004+6200G>A		intron_variant, non_coding_transcript_variant
LOC102723512	XR_007095787.1	n.1210+4127G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000661097.1	n.450+4127G>A		intron_variant, non_coding_transcript_variant
SUMF1	ENST00000448413.5	c.1191+34317C>T		intron_variant, NMD_transcript_variant		2		ENSP00000404384
	ENST00000654218.1	n.59+6200G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133745 AN: 152002 Hom.: 59287 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.926

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.977

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.920

Gnomad OTH AF: 0.906

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.880 AC: 133838 AN: 152120 Hom.: 59322 Cov.: 32 AF XY: 0.882 AC XY: 65606 AN XY: 74360

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.926

Gnomad4 ASJ AF: 0.925

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.977

Gnomad4 FIN AF: 0.892

Gnomad4 NFE AF: 0.920

Gnomad4 OTH AF: 0.904

Alfa AF: 0.891 Hom.: 10251

Bravo AF: 0.874

Asia WGS AF: 0.965 AC: 3356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs317608; hg19: chr3-4075936;