8-86507007-C-G

Variant names:

• chr8-86507007-C-G
• rs778449680
• NM_016033.3:c.235G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016033.3(RMDN1):​c.235G>C​(p.Ala79Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000278 in 1,436,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A79T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: RMDN1 NM_016033.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39814934).

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.235G>C	p.Ala79Pro	missense	Exon 2 of 10	NP_057117.2	Q96DB5-1
	RMDN1	NM_001286719.2		c.235G>C	p.Ala79Pro	missense	Exon 2 of 9	NP_001273648.1	Q96DB5-2
	RMDN1	NM_001286707.2		c.235G>C	p.Ala79Pro	missense	Exon 2 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.235G>C	p.Ala79Pro	missense	Exon 2 of 10	ENSP00000385927.3	Q96DB5-1
	RMDN1	ENST00000902721.1		c.235G>C	p.Ala79Pro	missense	Exon 2 of 11	ENSP00000572780.1
	RMDN1	ENST00000902719.1		c.277G>C	p.Ala93Pro	missense	Exon 2 of 10	ENSP00000572778.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000278 AC: 4 AN: 1436334 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 716310

African (AFR) AF: 0.00 AC: 0 AN: 32978

American (AMR) AF: 0.00 AC: 0 AN: 44586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25954

East Asian (EAS) AF: 0.00 AC: 0 AN: 39570

South Asian (SAS) AF: 0.00 AC: 0 AN: 85678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 9.18e-7 AC: 1 AN: 1088956

Other (OTH) AF: 0.0000504 AC: 3 AN: 59502

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.40	T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.3
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.29
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.020	D
Polyphen		0.97	D
Vest4		0.45
MVP		0.75
MPC		0.35
ClinPred		0.96	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.58
gMVP		0.66
Mutation Taster		=56/44	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: rs778449680; hg19: chr8-87519236;