2-238068129-A-C

Variant names:

• chr2-238068129-A-C
• rs144982752
• NM_016510.7:c.267A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016510.7(SCLY):​c.267A>C​(p.Lys89Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,611,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: SCLY NM_016510.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425
• Publications: 1 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: 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=0.10144538).

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.267A>C	p.Lys89Asn	missense	Exon 3 of 12	NP_057594.5
	UBE2F-SCLY	NR_037904.1		n.843A>C		non_coding_transcript_exon	Exon 10 of 19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCLY	ENST00000254663.12	TSL:1 MANE Select	c.267A>C	p.Lys89Asn	missense	Exon 3 of 12	ENSP00000254663.7	Q96I15-1
	SCLY	ENST00000409736.6	TSL:1	c.267A>C	p.Lys89Asn	missense	Exon 3 of 8	ENSP00000387162.2	Q96I15-2
	UBE2F-SCLY	ENST00000449191.1	TSL:3	n.*440A>C		non_coding_transcript_exon	Exon 11 of 11	ENSP00000456827.1	H3BSR4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000161 AC: 4 AN: 248332 AF XY: 0.0000223

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000754 AC: 11 AN: 1459122 Hom.: 0 Cov.: 29 AF XY: 0.0000124 AC XY: 9 AN XY: 725820

African (AFR) AF: 0.00 AC: 0 AN: 33386

American (AMR) AF: 0.00 AC: 0 AN: 44292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39534

South Asian (SAS) AF: 0.000117 AC: 10 AN: 85490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110846

Other (OTH) AF: 0.00 AC: 0 AN: 60294

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152218 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74362

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	1.8
DANN	Benign	0.82
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.42
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.090
Sift	Benign	0.19	T
Sift4G	Benign	0.42	T
Polyphen		0.0040	B
Vest4		0.26
MutPred		0.47		Loss of methylation at K89 (P = 0.0142)
MVP		0.35
MPC		0.091
ClinPred		0.036	T
GERP RS		-4.1
Mutation Taster		=71/29	polymorphism

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: rs144982752; hg19: chr2-238976770;