8-86508550-G-T

Variant names:

• chr8-86508550-G-T
• rs200923808
• NM_016033.3:c.71C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016033.3(RMDN1):​c.71C>A​(p.Pro24His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. P24L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RMDN1 NM_016033.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08600831).

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.71C>A	p.Pro24His	missense	Exon 1 of 10	NP_057117.2	Q96DB5-1
	RMDN1	NM_001286719.2		c.71C>A	p.Pro24His	missense	Exon 1 of 9	NP_001273648.1	Q96DB5-2
	RMDN1	NM_001286707.2		c.71C>A	p.Pro24His	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.71C>A	p.Pro24His	missense	Exon 1 of 10	ENSP00000385927.3	Q96DB5-1
	RMDN1	ENST00000902721.1		c.71C>A	p.Pro24His	missense	Exon 1 of 11	ENSP00000572780.1
	RMDN1	ENST00000902719.1		c.71C>A	p.Pro24His	missense	Exon 1 of 10	ENSP00000572778.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1441006 Hom.: 0 Cov.: 30 AF XY: 0.00000280 AC XY: 2 AN XY: 715314

African (AFR) AF: 0.00 AC: 0 AN: 33146

American (AMR) AF: 0.00 AC: 0 AN: 42132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25666

East Asian (EAS) AF: 0.00 AC: 0 AN: 38864

South Asian (SAS) AF: 0.00 AC: 0 AN: 83668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5320

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1104124

Other (OTH) AF: 0.00 AC: 0 AN: 59632

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.9
DANN	Benign	0.87
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.17
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.031
Sift	Benign	0.050	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.22	B
Vest4		0.14
MutPred		0.26		Gain of MoRF binding (P = 0.049)
MVP		0.13
MPC		0.19
ClinPred		0.81	D
GERP RS		-7.7
PromoterAI		0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.052
gMVP		0.35
Mutation Taster		=97/3	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: rs200923808; hg19: chr8-87520779;