6-30062412-T-C

Variant names:

• chr6-30062412-T-C
• rs9261271
• NM_170783.4:c.356+79T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_170783.4(POLR1H):​c.356+79T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000122 in 821,722 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: POLR1H NM_170783.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130

Genes affected

POLR1H (HGNC:13182): (RNA polymerase I subunit H) This gene encodes a DNA-directed RNA polymerase I subunit. The encoded protein contains two potential zinc-binding motifs and may play a role in regulation of cell proliferation. The encoded protein may be involved in cancer and human immunodeficiency virus progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

PPP1R11 (HGNC:9285): (protein phosphatase 1 regulatory inhibitor subunit 11) This gene encodes a specific inhibitor of protein phosphatase-1 (PP1) with a differential sensitivity toward the metal-independent and metal-dependent forms of PP1. The gene is located within the major histocompatibility complex class I region on chromosome 6. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1H	NM_170783.4	c.356+79T>C		intron_variant	Intron 3 of 3	ENST00000332435.10	NP_740753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR1H	ENST00000332435.10	c.356+79T>C		intron_variant	Intron 3 of 3	1	NM_170783.4	ENSP00000331111.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000122 AC: 1 AN: 821722 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 425902

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

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
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.56

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: rs9261271; hg19: chr6-30030189;