Genetic Variant SCLY:c.-6G>T (chr2-238061049-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016510.7(SCLY):c.-6G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000244 in 1,230,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

SCLY
NM_016510.7 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.853

Publications

0 publications found

Variant links:

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]

SCLY links:

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]

UBE2F-SCLY links:

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ACMG classification

Classification was made for transcript

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=0.10419941).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCLY	NM_016510.7	MANE Select	c.-6G>T		5_prime_UTR	Exon 1 of 12	NP_057594.5
	UBE2F-SCLY	NR_037904.1		n.666-3308G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCLY	ENST00000254663.12	TSL:1 MANE Select	c.-6G>T	5_prime_UTR	Exon 1 of 12	ENSP00000254663.7	Q96I15-1
SCLY	ENST00000409736.6	TSL:1	c.-6G>T	5_prime_UTR	Exon 1 of 8	ENSP00000387162.2	Q96I15-2
SCLY	ENST00000480357.5	TSL:1	n.122G>T	non_coding_transcript_exon	Exon 1 of 11

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000244

AC:

AN:

1230428

Hom.:

Cov.:

AF XY:

0.00000167

AC XY:

AN XY:

597082

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23816

American (AMR)

AF:

0.00

AC:

AN:

11676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17174

East Asian (EAS)

AF:

0.00

AC:

AN:

27608

South Asian (SAS)

AF:

0.00

AC:

AN:

56842

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3514

European-Non Finnish (NFE)

AF:

0.00000297

AC:

AN:

1009548

Other (OTH)

AF:

0.00

AC:

AN:

50772

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

1.6

(source)

DANN

Benign

0.93

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.32

M_CAP

Benign

0.00059

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

PhyloP100

-0.85

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.21

REVEL

Benign

0.011

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.11

MutPred

0.17

Gain of glycosylation at A7 (P = 0.0015)

MVP

0.18

MPC

0.24

ClinPred

0.18

GERP RS

-1.3

PromoterAI

0.094

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=95/5

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over