chr22-41526182-GCTGC-G

Position:

• chr22-41526182-GCTGC-G

Variant summary

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

The NM_001018050.4(POLR3H):​c.*3097_*3100del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,382,134 control chromosomes in the GnomAD database, including 33,075 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3334 hom., cov: 29)
  • Exomes 𝑓: 0.21 (29741 hom.)
• Consequence: POLR3H NM_001018050.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.888

Genes affected

POLR3H (HGNC:30349): (RNA polymerase III subunit H) Enables DNA-directed 5'-3' RNA polymerase activity. Involved in transcription by RNA polymerase III. Located in centrosome and nucleoplasm. Part of RNA polymerase III complex. [provided by Alliance of Genome Resources, Apr 2022]

ACO2 (HGNC:118): (aconitase 2) The protein encoded by this gene belongs to the aconitase/IPM isomerase family. It is an enzyme that catalyzes the interconversion of citrate to isocitrate via cis-aconitate in the second step of the TCA cycle. This protein is encoded in the nucleus and functions in the mitochondrion. It was found to be one of the mitochondrial matrix proteins that are preferentially degraded by the serine protease 15(PRSS15), also known as Lon protease, after oxidative modification. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 22-41526182-GCTGC-G is Benign according to our data. Variant chr22-41526182-GCTGC-G is described in ClinVar as [Benign]. Clinvar id is 1280168.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR3H	NM_001018050.4	c.*3097_*3100del		3_prime_UTR_variant	6/6	ENST00000355209.9	NP_001018060.1
ACO2	NM_001098.3	c.1762-73_1762-70del		intron_variant		ENST00000216254.9	NP_001089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR3H	ENST00000355209.9	c.*3097_*3100del		3_prime_UTR_variant	6/6	1	NM_001018050.4	ENSP00000347345	P1
ACO2	ENST00000216254.9	c.1762-73_1762-70del		intron_variant		1	NM_001098.3	ENSP00000216254	P3

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26723 AN: 151802 Hom.: 3329 Cov.: 29

Gnomad AFR AF: 0.0503

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.206 AC: 252892 AN: 1230214 Hom.: 29741 AF XY: 0.209 AC XY: 127428 AN XY: 610614

Gnomad4 AFR exome AF: 0.0451

Gnomad4 AMR exome AF: 0.521

Gnomad4 ASJ exome AF: 0.276

Gnomad4 EAS exome AF: 0.0486

Gnomad4 SAS exome AF: 0.307

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.194

Gnomad4 OTH exome AF: 0.206

GnomAD4 genome AF: 0.176 AC: 26730 AN: 151920 Hom.: 3334 Cov.: 29 AF XY: 0.185 AC XY: 13730 AN XY: 74248

Gnomad4 AFR AF: 0.0502

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.0528

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.201

Alfa AF: 0.178 Hom.: 362

Bravo AF: 0.184

Asia WGS AF: 0.153 AC: 534 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 06, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs71772435; hg19: chr22-41922186;