Variant 15-40745020-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000338376.8(RMDN3):c.764G>C(p.Gly255Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RMDN3
ENST00000338376.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.326

Variant links:

Genes affected

RMDN3 (HGNC:25550): (regulator of microtubule dynamics 3) Enables microtubule binding activity. Involved in cellular calcium ion homeostasis. Located in several cellular components, including intercellular bridge; mitochondrial outer membrane; and spindle. [provided by Alliance of Genome Resources, Apr 2022]

RMDN3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.033034056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RMDN3	NM_018145.3 linkuse as main transcript	c.764G>C	p.Gly255Ala	missense_variant	5/13	ENST00000338376.8	NP_060615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RMDN3	ENST00000338376.8 linkuse as main transcript	c.764G>C	p.Gly255Ala	missense_variant	5/13	1	NM_018145.3	ENSP00000342493	P1	Q96TC7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250304

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135378

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460080

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726028

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.764G>C (p.G255A) alteration is located in exon 5 (coding exon 4) of the RMDN3 gene. This alteration results from a G to C substitution at nucleotide position 764, causing the glycine (G) at amino acid position 255 to be replaced by an alanine (A). 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

0.082

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.3

DANN

Benign

0.46

DEOGEN2

Benign

0.013

T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Uncertain

0.86

.;D;D

M_CAP

Benign

0.0087

MetaRNN

Benign

0.033

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.88

N;N;N

REVEL

Benign

0.032

Sift

Benign

0.60

T;T;T

Sift4G

Benign

0.59

T;T;.

Polyphen

0.0040

B;B;.

Vest4

0.24

MutPred

0.28

Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);

MVP

0.040

MPC

0.18

ClinPred

0.011

GERP RS

-3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.053

gMVP

0.083

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over