8-86473939-T-C

Position:

• chr8-86473939-T-C

Variant summary

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

The NM_016033.3(RMDN1):​c.*369A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,007,086 control chromosomes in the GnomAD database, including 35,565 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 0.27 (6466 hom., cov: 32)
  • Exomes 𝑓: 0.26 (29099 hom.)
• Consequence: RMDN1 NM_016033.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

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]

RMDN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RMDN1	NM_016033.3	c.*369A>G		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	c.*369A>G		3_prime_UTR_variant	10/10	1	NM_016033.3	ENSP00000385927.3

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41272 AN: 151892 Hom.: 6445 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.257 AC: 219771 AN: 855076 Hom.: 29099 Cov.: 30 AF XY: 0.257 AC XY: 101883 AN XY: 396236

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.523

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.535

Gnomad4 SAS exome AF: 0.384

Gnomad4 FIN exome AF: 0.246

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.280

GnomAD4 genome AF: 0.272 AC: 41316 AN: 152010 Hom.: 6466 Cov.: 32 AF XY: 0.280 AC XY: 20809 AN XY: 74288

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.306

Alfa AF: 0.277 Hom.: 7958

Bravo AF: 0.285

Asia WGS AF: 0.445 AC: 1546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs4961193; hg19: chr8-87486168;