rs17353856

chr10-14899655-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001193424.2(SUV39H2):c.966C>T(p.Tyr322=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,613,652 control chromosomes in the GnomAD database, including 13,659 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 0.095 (882 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12777 hom.)
• Consequence: SUV39H2 NM_001193424.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=0.128 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUV39H2	NM_001193424.2	c.966C>T	p.Tyr322=	synonymous_variant	4/6	ENST00000354919.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUV39H2	ENST00000354919.11	c.966C>T	p.Tyr322=	synonymous_variant	4/6	5	NM_001193424.2	P1

Frequencies

GnomAD3 genomes AF: 0.0954 AC: 14515 AN: 152096 Hom.: 882 Cov.: 32

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.00288

Gnomad SAS AF: 0.0813

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.0957

GnomAD3 exomes AF: 0.105 AC: 26228 AN: 250970 Hom.: 1626 AF XY: 0.105 AC XY: 14255 AN XY: 135642

Gnomad AFR exome AF: 0.0291

Gnomad AMR exome AF: 0.114

Gnomad ASJ exome AF: 0.0708

Gnomad EAS exome AF: 0.00245

Gnomad SAS exome AF: 0.0859

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.0996

GnomAD4 exome AF: 0.128 AC: 186402 AN: 1461438 Hom.: 12777 Cov.: 32 AF XY: 0.126 AC XY: 91663 AN XY: 727000

Gnomad4 AFR exome AF: 0.0274

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.0673

Gnomad4 EAS exome AF: 0.00224

Gnomad4 SAS exome AF: 0.0882

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.141

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.0953 AC: 14512 AN: 152214 Hom.: 882 Cov.: 32 AF XY: 0.0957 AC XY: 7124 AN XY: 74406

Gnomad4 AFR AF: 0.0310

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0706

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.0809

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.0961

Alfa AF: 0.117 Hom.: 746

Bravo AF: 0.0899

Asia WGS AF: 0.0430 AC: 149 AN: 3478

EpiCase AF: 0.129

EpiControl AF: 0.128

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	5.7
Dann	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs17353856; hg19: chr10-14941654;