rs387907020

Variant names:

• chr6-43521238-A-G
• NM_203290.4:c.979A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-43521238-A-G
• chr6-43521238-A-T

Variant summary

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

The NM_203290.4(POLR1C):​c.979A>G​(p.Lys327Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,492 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: POLR1C NM_203290.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.79

Genes affected

POLR1C (HGNC:20194): (RNA polymerase I and III subunit C) The protein encoded by this gene is a subunit of both RNA polymerase I and RNA polymerase III complexes. The encoded protein is part of the Pol core element. Mutations in this gene have been associated with Treacher Collins syndrome (TCS) and hypomyelinating leukodystrophy 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1C	NM_203290.4	c.979A>G	p.Lys327Glu	missense_variant	Exon 9 of 9	ENST00000642195.1	NP_976035.1
POLR1C	NM_001318876.2	c.922+190A>G		intron_variant	Intron 8 of 8		NP_001305805.1
POLR1C	NM_001363658.2	c.922+190A>G		intron_variant	Intron 8 of 9		NP_001350587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR1C	ENST00000642195.1	c.979A>G	p.Lys327Glu	missense_variant	Exon 9 of 9		NM_203290.4	ENSP00000496044.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461492 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727058

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: 8.99e-7

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	0.29
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.76	.;D;.;D;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;.;.;D;D
M_CAP	Benign	0.070	D
MetaRNN	Uncertain	0.72	D;D;D;D;D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Benign	1.3	.;L;.;L;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.5	.;N;D;.;.
REVEL	Uncertain	0.58
Sift	Uncertain	0.012	.;D;D;.;.
Sift4G	Uncertain	0.060	.;T;T;.;.
Polyphen		0.87	.;P;.;P;.
Vest4		0.61, 0.64
MutPred		0.46		.;Loss of catalytic residue at K327 (P = 0.0166);.;Loss of catalytic residue at K327 (P = 0.0166);.;
MVP		0.85
MPC		0.16
ClinPred		0.96	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.71
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-43488976;