4-25159110-TAAA-TAAAAAA

Position:

• chr4-25159110-TAAA-TAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_016955.4(SEPSECS):​c.115-6_115-4dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,456,988 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000071 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0015 (0 hom.)
• Consequence: SEPSECS NM_016955.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00154 (2027/1315832) while in subpopulation AFR AF= 0.00329 (91/27694). AF 95% confidence interval is 0.00274. There are 0 homozygotes in gnomad4_exome. There are 972 alleles in male gnomad4_exome subpopulation. Median coverage is 22. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPSECS	NM_016955.4	c.115-6_115-4dupTTT		splice_region_variant, intron_variant		ENST00000382103.7	NP_058651.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPSECS	ENST00000382103.7	c.115-6_115-4dupTTT		splice_region_variant, intron_variant		1	NM_016955.4	ENSP00000371535.2

Frequencies

GnomAD3 genomes AF: 0.00000708 AC: 1 AN: 141156 Hom.: 0 Cov.: 26

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: 0.00

Gnomad FIN AF: 0.000119

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00154 AC: 2027 AN: 1315832 Hom.: 0 Cov.: 22 AF XY: 0.00149 AC XY: 972 AN XY: 654292

Gnomad4 AFR exome AF: 0.00329

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.00152

Gnomad4 EAS exome AF: 0.00154

Gnomad4 SAS exome AF: 0.00209

Gnomad4 FIN exome AF: 0.000416

Gnomad4 NFE exome AF: 0.00152

Gnomad4 OTH exome AF: 0.00149

GnomAD4 genome AF: 0.00000708 AC: 1 AN: 141156 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 68344

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000119

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34423002; hg19: chr4-25160732;