rs35131064

Positions:

• chr6-44204326-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318876.2(POLR1C):​c.946-237564C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,008 control chromosomes in the GnomAD database, including 3,283 homozygotes. 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: 𝑓 0.19 (3283 hom., cov: 31)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266

Genes affected

MYMX (HGNC:52391): (myomixer, myoblast fusion factor) Predicted to be involved in myoblast fusion involved in skeletal muscle regeneration; plasma membrane fusion; and skeletal muscle organ development. Predicted to be integral component of plasma membrane. Predicted to be active in Golgi membrane; endoplasmic reticulum membrane; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYMX	XM_024446300.2	c.-824C>T		5_prime_UTR_variant	2/4		XP_024302068.1
POLR1C	NM_001318876.2	c.946-237564C>T		intron_variant			NP_001305805.1
		n.44204326C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29461 AN: 151890 Hom.: 3285 Cov.: 31

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.231

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.194 AC: 29477 AN: 152008 Hom.: 3283 Cov.: 31 AF XY: 0.191 AC XY: 14154 AN XY: 74282

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.0232

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.231

Alfa AF: 0.221 Hom.: 946

Bravo AF: 0.188

Asia WGS AF: 0.123 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.1
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35131064; hg19: chr6-44172063;