4-25159110-TAAAAA-TAAAA

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_016955.4(SEPSECS):​c.115-4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 1,435,624 control chromosomes in the GnomAD database, including 188 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (181 hom., cov: 26)
  • Exomes 𝑓: 0.047 (7 hom.)
• Consequence: SEPSECS NM_016955.4 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• 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 -10 ACMG points.

• BP6: Variant 4-25159110-TA-T is Benign according to our data. Variant chr4-25159110-TA-T is described in ClinVar as [Benign]. Clinvar id is 1296157.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-25159110-TA-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0943 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 5680 AN: 141002 Hom.: 181 Cov.: 26

Gnomad AFR AF: 0.0968

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.0773

Gnomad EAS AF: 0.00609

Gnomad SAS AF: 0.0303

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.0357

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0354

GnomAD4 exome AF: 0.0469 AC: 60715 AN: 1294540 Hom.: 7 Cov.: 22 AF XY: 0.0466 AC XY: 30012 AN XY: 643802

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.0523

Gnomad4 ASJ exome AF: 0.0938

Gnomad4 EAS exome AF: 0.0245

Gnomad4 SAS exome AF: 0.0558

Gnomad4 FIN exome AF: 0.0403

Gnomad4 NFE exome AF: 0.0445

Gnomad4 OTH exome AF: 0.0519

GnomAD4 genome AF: 0.0404 AC: 5694 AN: 141084 Hom.: 181 Cov.: 26 AF XY: 0.0402 AC XY: 2749 AN XY: 68346

Gnomad4 AFR AF: 0.0969

Gnomad4 AMR AF: 0.0155

Gnomad4 ASJ AF: 0.0773

Gnomad4 EAS AF: 0.00610

Gnomad4 SAS AF: 0.0304

Gnomad4 FIN AF: 0.0194

Gnomad4 NFE AF: 0.0159

Gnomad4 OTH AF: 0.0350

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

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

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;