NM_173079.5:c.141G>T

Variant names:

• chr17-42980717-G-T
• rs372831938
• NM_173079.5:c.141G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_173079.5(RUNDC1):​c.141G>T​(p.Ala47Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,602 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. Synonymous variant affecting the same amino acid position (i.e. A47A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: RUNDC1 NM_173079.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 0 publications found

Genes affected

RUNDC1 (HGNC:25418): (RUN domain containing 1) This gene encodes a protein that contains a RUN (RPIP8, UNC-14 and NESCA) domain and a coiled coil domain. The encoded protein may negatively regulate p53 transcriptional activity. This gene is a potential candidate gene for predisposition to glioma in humans. [provided by RefSeq, May 2017]

PTGES3L-AARSD1 (HGNC:43946): (PTGES3L-AARSD1 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring PTGES3L (prostaglandin E synthase 3 (cytosolic)-like) and AARSD1(alanyl-tRNA synthetase domain containing 1) genes on chromosome 17. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=-0.079 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNDC1	NM_173079.5	c.141G>T	p.Ala47Ala	synonymous_variant	Exon 1 of 5	ENST00000361677.6	NP_775102.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNDC1	ENST00000361677.6	c.141G>T	p.Ala47Ala	synonymous_variant	Exon 1 of 5	1	NM_173079.5	ENSP00000354622.1
PTGES3L-AARSD1	ENST00000421990.7	c.-664C>A		upstream_gene_variant		2		ENSP00000409924.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396602 Hom.: 0 Cov.: 75 AF XY: 0.00000145 AC XY: 1 AN XY: 689980

African (AFR) AF: 0.00 AC: 0 AN: 31408

American (AMR) AF: 0.00 AC: 0 AN: 35604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24884

East Asian (EAS) AF: 0.00 AC: 0 AN: 35934

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79998

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4060

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1082720

Other (OTH) AF: 0.00 AC: 0 AN: 57984

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		-0.079
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs372831938; hg19: chr17-41132734;