NM_016033.3:c.130G>C

Variant names:

• chr8-86507112-C-G
• NM_016033.3:c.130G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016033.3(RMDN1):​c.130G>C​(p.Val44Leu) variant causes a missense, splice region 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. 13/23 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RMDN1 NM_016033.3 missense, splice_region
• Scores: Splicing: ADA: 0.9891
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMDN1	NM_016033.3	c.130G>C	p.Val44Leu	missense_variant, splice_region_variant	Exon 2 of 10	ENST00000406452.8	NP_057117.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMDN1	ENST00000406452.8	c.130G>C	p.Val44Leu	missense_variant, splice_region_variant	Exon 2 of 10	1	NM_016033.3	ENSP00000385927.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.130G>C (p.V44L) alteration is located in exon 2 (coding exon 2) of the RMDN1 gene. This alteration results from a G to C substitution at nucleotide position 130, causing the valine (V) at amino acid position 44 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T;.;.
Eigen	Benign	-0.11
Eigen_PC	Benign	0.021
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.22	N;N;N
REVEL	Benign	0.027
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.47	T;T;T
Polyphen		0.038	B;.;.
Vest4		0.33
MutPred		0.45		Gain of disorder (P = 0.065);Gain of disorder (P = 0.065);Gain of disorder (P = 0.065);
MVP		0.57
MPC		0.063
ClinPred		0.39	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.051
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.86
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-87519341;