rs13042

Positions:

• chr8-86472684-G-A
• chr8-86472684-G-T

Variant summary

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

The NM_016033.3(RMDN1):​c.*1624C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 531,410 control chromosomes in the GnomAD database, including 30,405 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 0.34 (9239 hom., cov: 31)
  • Exomes 𝑓: 0.32 (21166 hom.)
• Consequence: RMDN1 NM_016033.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

Genes affected

RMDN1 (HGNC:24285): (regulator of microtubule dynamics 1) Enables microtubule binding activity. Predicted to be involved in attachment of mitotic spindle microtubules to kinetochore and mitotic spindle organization. Located in mitotic spindle pole and spindle microtubule. [provided by Alliance of Genome Resources, Apr 2022]

WWP1 (HGNC:17004): (WW domain containing E3 ubiquitin protein ligase 1) WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing. This gene encodes a protein which contains 4 tandem WW domains and a HECT (homologous to the E6-associated protein carboxyl terminus) domain. The encoded protein belongs to a family of NEDD4-like proteins, which are E3 ubiquitin-ligase molecules and regulate key trafficking decisions, including targeting of proteins to proteosomes or lysosomes. Alternative splicing of this gene generates at least 6 transcript variants; however, the full length nature of these transcripts has not been defined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RMDN1	NM_016033.3	c.*1624C>T		3_prime_UTR_variant	10/10	ENST00000406452.8	NP_057117.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RMDN1	ENST00000406452.8	c.*1624C>T		3_prime_UTR_variant	10/10	1	NM_016033.3	ENSP00000385927	P1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51151 AN: 151174 Hom.: 9211 Cov.: 31

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.351

GnomAD4 exome AF: 0.318 AC: 120861 AN: 380118 Hom.: 21166 Cov.: 0 AF XY: 0.320 AC XY: 63839 AN XY: 199376

Gnomad4 AFR exome AF: 0.332

Gnomad4 AMR exome AF: 0.518

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.539

Gnomad4 SAS exome AF: 0.401

Gnomad4 FIN exome AF: 0.297

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.320

GnomAD4 genome AF: 0.339 AC: 51225 AN: 151292 Hom.: 9239 Cov.: 31 AF XY: 0.348 AC XY: 25711 AN XY: 73852

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.355

Alfa AF: 0.300 Hom.: 6236

Bravo AF: 0.351

Asia WGS AF: 0.492 AC: 1708 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.89
DANN	Benign	0.14

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

Publications

LitVar

Other links and lift over

dbSNP: rs13042; hg19: chr8-87484913;