NM_016955.4:c.115-4dupT

Variant names:

• chr4-25159110-T-TA
• rs34423002
• NM_016955.4:c.115-4dupT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_016955.4(SEPSECS):​c.115-4dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 140,886 control chromosomes in the GnomAD database, including 2,602 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2602 hom., cov: 26)
  • Exomes 𝑓: 0.38 (141 hom.)
  • Failed GnomAD Quality Control
• Consequence: SEPSECS NM_016955.4 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• 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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 4-25159110-T-TA is Benign according to our data. Variant chr4-25159110-T-TA is described in ClinVar as [Benign]. Clinvar id is 212150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPSECS	NM_016955.4	c.115-4dupT		splice_region_variant, intron_variant	Intron 1 of 10	ENST00000382103.7	NP_058651.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPSECS	ENST00000382103.7	c.115-4dupT		splice_region_variant, intron_variant	Intron 1 of 10	1	NM_016955.4	ENSP00000371535.2

Frequencies

GnomAD3 genomes AF: 0.183 AC: 25816 AN: 140810 Hom.: 2603 Cov.: 26

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0973

Gnomad MID AF: 0.192

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.194

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.382 AC: 461716 AN: 1209870 Hom.: 141 Cov.: 22 AF XY: 0.382 AC XY: 229495 AN XY: 601002

Gnomad4 AFR exome AF: 0.367

Gnomad4 AMR exome AF: 0.354

Gnomad4 ASJ exome AF: 0.362

Gnomad4 EAS exome AF: 0.405

Gnomad4 SAS exome AF: 0.374

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.384

Gnomad4 OTH exome AF: 0.382

GnomAD4 genome AF: 0.183 AC: 25845 AN: 140886 Hom.: 2602 Cov.: 26 AF XY: 0.183 AC XY: 12457 AN XY: 68224

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.0973

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.193

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 04, 2014

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Pontocerebellar hypoplasia type 2D Benign:1

Sep 27, 2019

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:1

Aug 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs34423002; hg19: chr4-25160732;