chr13-50910116-C-G

Position:

• chr13-50910116-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024570.4(RNASEH2B):​c.40C>G​(p.Arg14Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,306,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: RNASEH2B NM_024570.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153

Genes affected

RNASEH2B (HGNC:25671): (ribonuclease H2 subunit B) RNase H2 is composed of a single catalytic subunit (A) and two non-catalytic subunits (B and C) and specifically degrades the RNA of RNA:DNA hybrids. The protein encoded by this gene is the non-catalytic B subunit of RNase H2, which is thought to play a role in DNA replication. Multiple transcript variants encoding different isoforms have been found for this gene. Defects in this gene are a cause of Aicardi-Goutieres syndrome type 2 (AGS2). [provided by RefSeq, Nov 2008]

RNASEH2B-AS1 (HGNC:39967): (RNASEH2B antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16788116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASEH2B	NM_024570.4	c.40C>G	p.Arg14Gly	missense_variant	1/11	ENST00000336617.8	NP_078846.2
RNASEH2B-AS1	NR_046552.1	n.230+367G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASEH2B	ENST00000336617.8	c.40C>G	p.Arg14Gly	missense_variant	1/11	1	NM_024570.4	ENSP00000337623	P3
RNASEH2B-AS1	ENST00000596992.5	n.112+367G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000153 AC: 2 AN: 1306918 Hom.: 0 Cov.: 31 AF XY: 0.00000156 AC XY: 1 AN XY: 642356

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000710

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.0022	T;.;.;.;.;.;.;.;.;.;.;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.68	T;T;T;T;T;T;T;T;T;T;T;T
M_CAP	Pathogenic	0.51	D
MetaRNN	Benign	0.17	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	1.4	L;L;.;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.12	N;N;.;.;.;.;.;.;.;.;.;.
REVEL	Benign	0.25
Sift	Benign	0.36	T;T;.;.;.;.;.;.;.;.;.;.
Sift4G	Benign	0.27	T;T;.;.;.;.;.;.;.;.;.;.
Polyphen		0.38	B;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.27
MutPred		0.59		Gain of catalytic residue at V11 (P = 0);Gain of catalytic residue at V11 (P = 0);Gain of catalytic residue at V11 (P = 0);Gain of catalytic residue at V11 (P = 0);Gain of catalytic residue at V11 (P = 0);Gain of catalytic residue at V11 (P = 0);Gain of catalytic residue at V11 (P = 0);Gain of catalytic residue at V11 (P = 0);Gain of catalytic residue at V11 (P = 0);Gain of catalytic residue at V11 (P = 0);Gain of catalytic residue at V11 (P = 0);Gain of catalytic residue at V11 (P = 0);
MVP		0.60
MPC		0.12
ClinPred		0.11	T
GERP RS		0.063
Varity_R		0.24
gMVP		0.17

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: rs900876937; hg19: chr13-51484252;