rs4961193

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-86473939-T-A
• chr8-86473939-T-C
• chr8-86473939-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016033.3(RMDN1):​c.*369A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

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>T		3_prime_UTR	Exon 10 of 10	NP_057117.2
	RMDN1	NM_001286719.2		c.*369A>T		3_prime_UTR	Exon 9 of 9	NP_001273648.1
	RMDN1	NM_001286707.2		c.*369A>T		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>T		3_prime_UTR	Exon 10 of 10	ENSP00000385927.3
	RMDN1	ENST00000523911.5	TSL:2	c.723+881A>T		intron	N/A	ENSP00000429899.1
	RMDN1	ENST00000519789.5	TSL:3	c.596-1460A>T		intron	N/A	ENSP00000428897.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 10050

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.9
DANN	Benign	0.70
PhyloP100		-0.25
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

Other links and lift over

dbSNP: rs4961193; hg19: chr8-87486168;