8-86508565-G-C

Variant names:

• chr8-86508565-G-C
• rs759329797
• NM_016033.3:c.56C>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.56C>G​(p.Pro19Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,600,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P19L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: RMDN1 NM_016033.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 0 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]

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 (MetaRNN=0.03861326).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMDN1	NM_016033.3	MANE Select	c.56C>G	p.Pro19Arg	missense	Exon 1 of 10	NP_057117.2	Q96DB5-1
	RMDN1	NM_001286719.2		c.56C>G	p.Pro19Arg	missense	Exon 1 of 9	NP_001273648.1	Q96DB5-2
	RMDN1	NM_001286707.2		c.56C>G	p.Pro19Arg	missense	Exon 1 of 9	NP_001273636.1	Q96DB5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMDN1	ENST00000406452.8	TSL:1 MANE Select	c.56C>G	p.Pro19Arg	missense	Exon 1 of 10	ENSP00000385927.3	Q96DB5-1
	RMDN1	ENST00000902721.1		c.56C>G	p.Pro19Arg	missense	Exon 1 of 11	ENSP00000572780.1
	RMDN1	ENST00000902719.1		c.56C>G	p.Pro19Arg	missense	Exon 1 of 10	ENSP00000572778.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000220 AC: 5 AN: 226894 AF XY: 0.0000320

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000123

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000979

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000235 AC: 34 AN: 1448662 Hom.: 0 Cov.: 30 AF XY: 0.0000208 AC XY: 15 AN XY: 719832

African (AFR) AF: 0.0000300 AC: 1 AN: 33306

American (AMR) AF: 0.0000918 AC: 4 AN: 43572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25856

East Asian (EAS) AF: 0.00 AC: 0 AN: 39236

South Asian (SAS) AF: 0.00 AC: 0 AN: 84754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5466

European-Non Finnish (NFE) AF: 0.0000244 AC: 27 AN: 1107642

Other (OTH) AF: 0.0000334 AC: 2 AN: 59846

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152228 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74382

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000829 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.15
DANN	Benign	0.71
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		-1.1
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.0050
Sift	Benign	0.45	T
Sift4G	Benign	0.61	T
Polyphen		0.0010	B
Vest4		0.088
MutPred		0.32		Gain of MoRF binding (P = 0.0038)
MVP		0.11
MPC		0.064
ClinPred		0.030	T
GERP RS		-6.2
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.018
gMVP		0.45
Mutation Taster		=98/2	polymorphism

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: rs759329797; hg19: chr8-87520794;