8-86473939-T-C

Variant names:

• chr8-86473939-T-C
• rs4961193
• NM_016033.3:c.*369A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016033.3. 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
	RMDN1	NM_016033.3	MANE Select	c.*369A>G		3_prime_UTR	Exon 10 of 10	NP_057117.2
	RMDN1	NM_001286719.2		c.*369A>G		3_prime_UTR	Exon 9 of 9	NP_001273648.1
	RMDN1	NM_001286707.2		c.*369A>G		3_prime_UTR	Exon 9 of 9	NP_001273636.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMDN1	ENST00000406452.8	TSL:1 MANE Select	c.*369A>G		3_prime_UTR	Exon 10 of 10	ENSP00000385927.3
	RMDN1	ENST00000902719.1		c.*369A>G		3_prime_UTR	Exon 10 of 10	ENSP00000572778.1
	RMDN1	ENST00000949087.1		c.*369A>G		3_prime_UTR	Exon 10 of 10	ENSP00000619146.1

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

African (AFR) AF: 0.164 AC: 2667 AN: 16250

American (AMR) AF: 0.523 AC: 1456 AN: 2784

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 1240 AN: 5704

East Asian (EAS) AF: 0.535 AC: 2611 AN: 4884

South Asian (SAS) AF: 0.384 AC: 7030 AN: 18320

European-Finnish (FIN) AF: 0.246 AC: 272 AN: 1106

Middle Eastern (MID) AF: 0.298 AC: 503 AN: 1686

European-Non Finnish (NFE) AF: 0.253 AC: 196019 AN: 775862

Other (OTH) AF: 0.280 AC: 7973 AN: 28480

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

African (AFR) AF: 0.178 AC: 7395 AN: 41460

American (AMR) AF: 0.459 AC: 7020 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3472

East Asian (EAS) AF: 0.536 AC: 2754 AN: 5136

South Asian (SAS) AF: 0.399 AC: 1922 AN: 4822

European-Finnish (FIN) AF: 0.263 AC: 2781 AN: 10568

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17729 AN: 67958

Other (OTH) AF: 0.306 AC: 647 AN: 2112

Alfa AF: 0.277 Hom.: 10050

Bravo AF: 0.285

Asia WGS AF: 0.445 AC: 1546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.70
PhyloP100		-0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs4961193; hg19: chr8-87486168;