4-25150252-A-T

Position:

• chr4-25150252-A-T

Variant summary

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

The ENST00000382103.7(SEPSECS):​c.804+1708T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,196 control chromosomes in the GnomAD database, including 28,402 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 0.60 (28402 hom., cov: 33)
• Consequence: SEPSECS ENST00000382103.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.955

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPSECS	NM_016955.4	c.804+1708T>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.804+1708T>A		intron_variant		1	NM_016955.4	ENSP00000371535	P1

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91792 AN: 152078 Hom.: 28405 Cov.: 33

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.603 AC: 91816 AN: 152196 Hom.: 28402 Cov.: 33 AF XY: 0.602 AC XY: 44818 AN XY: 74396

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.610

Alfa AF: 0.638 Hom.: 3886

Bravo AF: 0.592

Asia WGS AF: 0.501 AC: 1743 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.8
DANN	Benign	0.91

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: rs1035091; hg19: chr4-25151874;