rs821480

Variant names:

• chr2-238064186-T-C
• rs821480
• NM_016510.7:c.90-171T>C

Variant summary

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

The NM_016510.7(SCLY):​c.90-171T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 152,234 control chromosomes in the GnomAD database, including 56,438 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 0.86 (56438 hom., cov: 32)
• Consequence: SCLY NM_016510.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 4 publications found

Genes affected

SCLY (HGNC:18161): (selenocysteine lyase) Selenocysteine lyase (SCLY; EC 4.4.1.16) catalyzes the pyridoxal 5-prime phosphate-dependent conversion of L-selenocysteine to L-alanine and elemental selenium (Mihara et al., 2000 [PubMed 10692412]).[supplied by OMIM, Mar 2008]

UBE2F-SCLY (HGNC:48339): (UBE2F-SCLY readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring UBE2F (ubiquitin-conjugating enzyme E2F) and SCLY (selenocysteine lyase) genes on chromosome 2. The read-through transcript is a candidate for non-sense mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016510.7. 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
	SCLY	NM_016510.7	MANE Select	c.90-171T>C		intron	N/A	NP_057594.5
	UBE2F-SCLY	NR_037904.1		n.666-171T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCLY	ENST00000254663.12	TSL:1 MANE Select	c.90-171T>C		intron	N/A	ENSP00000254663.7
	SCLY	ENST00000409736.6	TSL:1	c.90-171T>C		intron	N/A	ENSP00000387162.2
	UBE2F-SCLY	ENST00000449191.1	TSL:3	n.*263-171T>C		intron	N/A	ENSP00000456827.1

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130833 AN: 152116 Hom.: 56390 Cov.: 32

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.911

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.873

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

GnomAD4 genome AF: 0.860 AC: 130939 AN: 152234 Hom.: 56438 Cov.: 32 AF XY: 0.862 AC XY: 64152 AN XY: 74424

African (AFR) AF: 0.894 AC: 37137 AN: 41518

American (AMR) AF: 0.853 AC: 13045 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.911 AC: 3162 AN: 3472

East Asian (EAS) AF: 0.971 AC: 5043 AN: 5194

South Asian (SAS) AF: 0.727 AC: 3505 AN: 4820

European-Finnish (FIN) AF: 0.895 AC: 9502 AN: 10614

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.834 AC: 56695 AN: 68018

Other (OTH) AF: 0.871 AC: 1835 AN: 2106

Alfa AF: 0.838 Hom.: 28853

Bravo AF: 0.862

Asia WGS AF: 0.832 AC: 2895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.27
DANN	Benign	0.51
PhyloP100		-1.6
Mutation Taster		=100/0	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: rs821480; hg19: chr2-238972827;