2-238068120-A-G

Variant names:

• chr2-238068120-A-G
• rs76625747
• NM_016510.7:c.258A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_016510.7(SCLY):​c.258A>G​(p.Ile86Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00266 in 1,611,698 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (41 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (56 hom.)
• Consequence: SCLY NM_016510.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.790

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0075370967).
• BP6: Variant 2-238068120-A-G is Benign according to our data. Variant chr2-238068120-A-G is described in ClinVar as [Benign]. Clinvar id is 785025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0138 (2104/152290) while in subpopulation AFR AF= 0.0481 (1998/41552). AF 95% confidence interval is 0.0463. There are 41 homozygotes in gnomad4. There are 976 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCLY	NM_016510.7	c.258A>G	p.Ile86Met	missense_variant	Exon 3 of 12	ENST00000254663.12	NP_057594.5
UBE2F-SCLY	NR_037904.1	n.834A>G		non_coding_transcript_exon_variant	Exon 10 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCLY	ENST00000254663.12	c.258A>G	p.Ile86Met	missense_variant	Exon 3 of 12	1	NM_016510.7	ENSP00000254663.7
UBE2F-SCLY	ENST00000449191.1	n.*431A>G		non_coding_transcript_exon_variant	Exon 11 of 11	3		ENSP00000456827.1
UBE2F-SCLY	ENST00000449191.1	n.*431A>G		3_prime_UTR_variant	Exon 11 of 11	3		ENSP00000456827.1

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2104 AN: 152172 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00956

GnomAD3 exomes AF: 0.00370 AC: 918 AN: 248434 Hom.: 21 AF XY: 0.00281 AC XY: 377 AN XY: 134260

Gnomad AFR exome AF: 0.0508

Gnomad AMR exome AF: 0.00195

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000671

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.000669

GnomAD4 exome AF: 0.00149 AC: 2176 AN: 1459408 Hom.: 56 Cov.: 30 AF XY: 0.00130 AC XY: 941 AN XY: 725900

Gnomad4 AFR exome AF: 0.0514

Gnomad4 AMR exome AF: 0.00223

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000211

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000110

Gnomad4 OTH exome AF: 0.00337

GnomAD4 genome AF: 0.0138 AC: 2104 AN: 152290 Hom.: 41 Cov.: 32 AF XY: 0.0131 AC XY: 976 AN XY: 74478

Gnomad4 AFR AF: 0.0481

Gnomad4 AMR AF: 0.00412

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00225 Hom.: 11

Bravo AF: 0.0160

ESP6500AA AF: 0.0463 AC: 204

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00465 AC: 564

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 02, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	14
DANN	Benign	0.94
Eigen	Benign	-0.87
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.71	T;T;T
MetaRNN	Benign	0.0075	T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.6	.;M;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Uncertain	0.50
Sift	Benign	0.068	T;T;T
Sift4G	Uncertain	0.041	D;D;T
Polyphen		0.60	.;P;.
Vest4		0.27
MVP		0.52
MPC		0.13
ClinPred		0.023	T
GERP RS		-10

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

LitVar

Other links and lift over

dbSNP: rs76625747; hg19: chr2-238976761;