rs7257575

Variant names:

• chr19-12810121-G-A
• rs7257575
• NM_006397.3:c.462G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-12810121-G-A
• chr19-12810121-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006397.3(RNASEH2A):​c.462G>A​(p.Gln154Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 1,614,120 control chromosomes in the GnomAD database, including 1,944 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.066 (534 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1410 hom.)
• Consequence: RNASEH2A NM_006397.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.281
• Publications: 6 publications found

Genes affected

RNASEH2A (HGNC:18518): (ribonuclease H2 subunit A) The protein encoded by this gene is a component of the heterotrimeric type II ribonuclease H enzyme (RNAseH2). RNAseH2 is the major source of ribonuclease H activity in mammalian cells and endonucleolytically cleaves ribonucleotides. It is predicted to remove Okazaki fragment RNA primers during lagging strand DNA synthesis and to excise single ribonucleotides from DNA-DNA duplexes. Mutations in this gene cause Aicardi-Goutieres Syndrome (AGS), a an autosomal recessive neurological disorder characterized by progressive microcephaly and psychomotor retardation, intracranial calcifications, elevated levels of interferon-alpha and white blood cells in the cerebrospinal fluid.[provided by RefSeq, Aug 2009]

THSD8 (HGNC:53785): (thrombospondin type 1 domain containing 8)

HOOK2 (HGNC:19885): (hook microtubule tethering protein 2) Hook proteins are cytosolic coiled-coil proteins that contain conserved N-terminal domains, which attach to microtubules, and more divergent C-terminal domains, which mediate binding to organelles. The Drosophila Hook protein is a component of the endocytic compartment.[supplied by OMIM, Apr 2004]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 19-12810121-G-A is Benign according to our data. Variant chr19-12810121-G-A is described in ClinVar as Benign. ClinVar VariationId is 259972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.281 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006397.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASEH2A	NM_006397.3	MANE Select	c.462G>A	p.Gln154Gln	synonymous	Exon 5 of 8	NP_006388.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASEH2A	ENST00000221486.6	TSL:1 MANE Select	c.462G>A	p.Gln154Gln	synonymous	Exon 5 of 8	ENSP00000221486.4	O75792
	RNASEH2A	ENST00000926045.1		c.432G>A	p.Gln144Gln	synonymous	Exon 5 of 8	ENSP00000596104.1
	RNASEH2A	ENST00000926044.1		c.414G>A	p.Gln138Gln	synonymous	Exon 5 of 8	ENSP00000596103.1

Frequencies

GnomAD3 genomes AF: 0.0660 AC: 10037 AN: 152120 Hom.: 530 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0700

Gnomad ASJ AF: 0.0426

Gnomad EAS AF: 0.0168

Gnomad SAS AF: 0.0273

Gnomad FIN AF: 0.0282

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0315

Gnomad OTH AF: 0.0554

GnomAD2 exomes AF: 0.0474 AC: 11921 AN: 251496 AF XY: 0.0427

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.109

Gnomad ASJ exome AF: 0.0433

Gnomad EAS exome AF: 0.0176

Gnomad FIN exome AF: 0.0275

Gnomad NFE exome AF: 0.0301

Gnomad OTH exome AF: 0.0397

GnomAD4 exome AF: 0.0368 AC: 53777 AN: 1461882 Hom.: 1410 Cov.: 33 AF XY: 0.0360 AC XY: 26202 AN XY: 727242

African (AFR) AF: 0.150 AC: 5026 AN: 33476

American (AMR) AF: 0.105 AC: 4712 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0420 AC: 1099 AN: 26136

East Asian (EAS) AF: 0.0110 AC: 438 AN: 39700

South Asian (SAS) AF: 0.0283 AC: 2445 AN: 86258

European-Finnish (FIN) AF: 0.0273 AC: 1460 AN: 53420

Middle Eastern (MID) AF: 0.0496 AC: 286 AN: 5768

European-Non Finnish (NFE) AF: 0.0322 AC: 35773 AN: 1112004

Other (OTH) AF: 0.0420 AC: 2538 AN: 60396

GnomAD4 genome AF: 0.0662 AC: 10071 AN: 152238 Hom.: 534 Cov.: 32 AF XY: 0.0653 AC XY: 4864 AN XY: 74440

African (AFR) AF: 0.145 AC: 6015 AN: 41508

American (AMR) AF: 0.0698 AC: 1066 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0426 AC: 148 AN: 3472

East Asian (EAS) AF: 0.0168 AC: 87 AN: 5178

South Asian (SAS) AF: 0.0277 AC: 134 AN: 4832

European-Finnish (FIN) AF: 0.0282 AC: 300 AN: 10620

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0315 AC: 2142 AN: 68026

Other (OTH) AF: 0.0553 AC: 117 AN: 2114

Alfa AF: 0.0479 Hom.: 215

Bravo AF: 0.0742

Asia WGS AF: 0.0320 AC: 110 AN: 3478

EpiCase AF: 0.0314

EpiControl AF: 0.0344

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Aicardi-Goutieres syndrome 4 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.7
DANN	Benign	0.58
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7257575; hg19: chr19-12920935; COSMIC: COSV55551829; COSMIC: COSV55551829;