4-25131742-C-T

Position:

• chr4-25131742-C-T

Variant summary

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

The NM_016955.4(SEPSECS):​c.1027-4385G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,176 control chromosomes in the GnomAD database, including 50,910 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 0.82 (50910 hom., cov: 32)
• Consequence: SEPSECS NM_016955.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

Genes affected

SEPSECS (HGNC:30605): (Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase) The amino acid selenocysteine is the only amino acid that does not have its own tRNA synthetase. Instead, this amino acid is synthesized on its cognate tRNA in a three step process. The protein encoded by this gene catalyzes the third step in the process, the conversion of O-phosphoseryl-tRNA(Sec) to selenocysteinyl-tRNA(Sec).[provided by RefSeq, Mar 2011]

SEPSECS (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPSECS	NM_016955.4	c.1027-4385G>A		intron_variant		ENST00000382103.7	NP_058651.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPSECS	ENST00000382103.7	c.1027-4385G>A		intron_variant		1	NM_016955.4	ENSP00000371535.2

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124349 AN: 152058 Hom.: 50888 Cov.: 32

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.830

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

GnomAD4 genome AF: 0.818 AC: 124420 AN: 152176 Hom.: 50910 Cov.: 32 AF XY: 0.817 AC XY: 60810 AN XY: 74388

Gnomad4 AFR AF: 0.822

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.849

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.845

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.821

Gnomad4 OTH AF: 0.828

Alfa AF: 0.824 Hom.: 7346

Bravo AF: 0.819

Asia WGS AF: 0.764 AC: 2659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.63

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: rs3756207; hg19: chr4-25133364;