NM_007055.4:c.4024+368G>A

Variant names:

• chr10-77979773-C-T
• rs4979936
• NM_007055.4:c.4024+368G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007055.4(POLR3A):​c.4024+368G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,102 control chromosomes in the GnomAD database, including 9,778 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 0.32 (9778 hom., cov: 32)
• Consequence: POLR3A NM_007055.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 1 publications found

Genes affected

POLR3A (HGNC:30074): (RNA polymerase III subunit A) The protein encoded by this gene is the catalytic component of RNA polymerase III, which synthesizes small RNAs. The encoded protein also acts as a sensor to detect foreign DNA and trigger an innate immune response. [provided by RefSeq, Aug 2011]

POLR3A Gene-Disease associations (from GenCC):

• odontoleukodystrophy

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Illumina, Orphanet
• Wiedemann-Rautenstrauch syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• tremor-ataxia-central hypomyelination syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007055.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR3A	NM_007055.4	MANE Select	c.4024+368G>A		intron	N/A	NP_008986.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR3A	ENST00000372371.8	TSL:1 MANE Select	c.4024+368G>A		intron	N/A	ENSP00000361446.3
	POLR3A	ENST00000698731.1		c.3883+368G>A		intron	N/A	ENSP00000513898.1
	POLR3A	ENST00000698724.1		n.1941+368G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48606 AN: 151984 Hom.: 9743 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.320 AC: 48699 AN: 152102 Hom.: 9778 Cov.: 32 AF XY: 0.319 AC XY: 23733 AN XY: 74362

African (AFR) AF: 0.555 AC: 23030 AN: 41462

American (AMR) AF: 0.284 AC: 4336 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 781 AN: 3470

East Asian (EAS) AF: 0.518 AC: 2667 AN: 5148

South Asian (SAS) AF: 0.297 AC: 1431 AN: 4824

European-Finnish (FIN) AF: 0.178 AC: 1887 AN: 10602

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13489 AN: 67996

Other (OTH) AF: 0.309 AC: 652 AN: 2110

Alfa AF: 0.243 Hom.: 1862

Bravo AF: 0.339

Asia WGS AF: 0.444 AC: 1541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.9
DANN	Benign	0.28
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs4979936; hg19: chr10-79739531;