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. The variant received -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
• Publications: 8 publications found

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]

POLR1HASP (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170783.4. 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
	POLR1H	NM_170783.4	MANE Select	c.356+79T>C		intron	N/A	NP_740753.1	Q9P1U0
	POLR1H	NM_001278785.2		c.356+79T>C		intron	N/A	NP_001265714.1	Q9P1U0
	POLR1H	NM_001278786.2		c.356+79T>C		intron	N/A	NP_001265715.1	Q9P1U0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR1H	ENST00000332435.10	TSL:1 MANE Select	c.356+79T>C		intron	N/A	ENSP00000331111.5	Q9P1U0
	POLR1H	ENST00000359374.8	TSL:1	c.356+79T>C		intron	N/A	ENSP00000352333.4	Q9P1U0
	POLR1H	ENST00000471008.5	TSL:1	n.3435+79T>C		intron	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 20864

American (AMR) AF: 0.00 AC: 0 AN: 36460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21290

East Asian (EAS) AF: 0.00 AC: 0 AN: 33776

South Asian (SAS) AF: 0.00 AC: 0 AN: 69428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4560

European-Non Finnish (NFE) AF: 0.00000181 AC: 1 AN: 551212

Other (OTH) AF: 0.00 AC: 0 AN: 39100

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.56
PhyloP100		-0.13

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: rs9261271; hg19: chr6-30030189;