ENST00000378289.8:c.1282C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000378289.8(DCLRE1C):c.1282C>T(p.Arg428Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 701,848 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 9 hom. )

Consequence

DCLRE1C
ENST00000378289.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0110

Variant links:

Genes affected

DCLRE1C (HGNC:17642): (DNA cross-link repair 1C) This gene encodes a nuclear protein that is involved in V(D)J recombination and DNA repair. The encoded protein has single-strand-specific 5'-3' exonuclease activity; it also exhibits endonuclease activity on 5' and 3' overhangs and hairpins. The protein also functions in the regulation of the cell cycle in response to DNA damage. Mutations in this gene can cause Athabascan-type severe combined immunodeficiency (SCIDA) and Omenn syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

DCLRE1C links:

SUV39H2 (HGNC:17287): (SUV39H2 histone lysine methyltransferase) Enables S-adenosyl-L-methionine binding activity; histone methyltransferase activity (H3-K9 specific); and zinc ion binding activity. Involved in chromatin assembly or disassembly and chromatin remodeling. Acts upstream of or within cellular response to hypoxia and negative regulation of transcription by RNA polymerase II. Located in chromatin. [provided by Alliance of Genome Resources, Apr 2022]

SUV39H2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052094758).

BP6

Variant 10-14899187-G-A is Benign according to our data. Variant chr10-14899187-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1694558.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00289 (440/152218) while in subpopulation NFE AF= 0.00406 (276/68008). AF 95% confidence interval is 0.00367. There are 3 homozygotes in gnomad4. There are 193 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUV39H2	NM_001193424.2 link	c.850-352G>A		intron_variant	Intron 3 of 5	ENST00000354919.11	NP_001180353.1	Q9H5I1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUV39H2	ENST00000354919.11 link	c.850-352G>A		intron_variant	Intron 3 of 5	5	NM_001193424.2	ENSP00000346997.6		Q9H5I1-1

Frequencies

GnomAD3 genomes

AF:

0.00289

AC:

440

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000661

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00406

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00343

AC:

438

AN:

127866

Hom.:

AF XY:

0.00356

AC XY:

249

AN XY:

70018

show subpopulations

Gnomad AFR exome

AF:

0.000986

Gnomad AMR exome

AF:

0.00292

Gnomad ASJ exome

AF:

0.0137

Gnomad EAS exome

AF:

0.000287

Gnomad SAS exome

AF:

0.00125

Gnomad FIN exome

AF:

0.000559

Gnomad NFE exome

AF:

0.00404

Gnomad OTH exome

AF:

0.00628

GnomAD4 exome

AF:

0.00344

AC:

1888

AN:

549630

Hom.:

Cov.:

AF XY:

0.00349

AC XY:

1039

AN XY:

297552

show subpopulations

Gnomad4 AFR exome

AF:

0.000570

Gnomad4 AMR exome

AF:

0.00294

Gnomad4 ASJ exome

AF:

0.0157

Gnomad4 EAS exome

AF:

0.000156

Gnomad4 SAS exome

AF:

0.00108

Gnomad4 FIN exome

AF:

0.000512

Gnomad4 NFE exome

AF:

0.00383

Gnomad4 OTH exome

AF:

0.00393

GnomAD4 genome

AF:

0.00289

AC:

440

AN:

152218

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

193

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000661

Gnomad4 NFE

AF:

0.00406

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00360

Hom.:

Bravo

AF:

0.00308

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00441

AC:

ExAC

AF:

0.00304

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DCLRE1C: BP4, BS2; SUV39H2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

7.7

DANN

Benign

0.41

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.38

REVEL

Benign

0.15

Sift

Pathogenic

0.0

Polyphen

0.0

Vest4

0.088

MVP

0.061

ClinPred

0.0026

GERP RS

-1.5

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over