Genetic Variant RMDN3:p.Arg257Gln (chr15-40745014-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018145.3(RMDN3):c.770G>A(p.Arg257Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,611,028 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

RMDN3
NM_018145.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.529

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.043503672).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018145.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RMDN3	NM_018145.3	MANE Select	c.770G>A	p.Arg257Gln	missense	Exon 5 of 13	NP_060615.1	Q96TC7-1
RMDN3	NM_001323896.2		c.770G>A	p.Arg257Gln	missense	Exon 5 of 13	NP_001310825.1
RMDN3	NM_001323897.2		c.770G>A	p.Arg257Gln	missense	Exon 5 of 13	NP_001310826.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RMDN3	ENST00000338376.8	TSL:1 MANE Select	c.770G>A	p.Arg257Gln	missense	Exon 5 of 13	ENSP00000342493.3	Q96TC7-1
RMDN3	ENST00000260385.10	TSL:1	c.770G>A	p.Arg257Gln	missense	Exon 4 of 12	ENSP00000260385.6	Q96TC7-1
RMDN3	ENST00000558777.5	TSL:2	n.*321G>A		non_coding_transcript_exon	Exon 6 of 14	ENSP00000453357.1	H0YLV7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000800

AC:

AN:

249886

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1458910

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725224

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33394

American (AMR)

AF:

0.00

AC:

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39598

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86200

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00000541

AC:

AN:

1109706

Other (OTH)

AF:

0.00

AC:

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41428

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.61

M_CAP

Benign

0.0060

MetaRNN

Benign

0.044

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.53

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.18

REVEL

Benign

0.010

Sift

Benign

0.41

Sift4G

Benign

0.37

Polyphen

0.069

Vest4

0.25

MVP

0.19

MPC

0.19

ClinPred

0.13

GERP RS

-0.10

PromoterAI

-0.0076

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.033

gMVP

0.093

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over