Genetic Variant RMDN3:p.Arg257Pro (chr15-40745014-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018145.3(RMDN3):c.770G>C(p.Arg257Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,611,146 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. R257Q) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RMDN3
NM_018145.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

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=0.21499032).

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>C	p.Arg257Pro	missense	Exon 5 of 13	NP_060615.1	Q96TC7-1
RMDN3	NM_001323896.2		c.770G>C	p.Arg257Pro	missense	Exon 5 of 13	NP_001310825.1
RMDN3	NM_001323897.2		c.770G>C	p.Arg257Pro	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>C	p.Arg257Pro	missense	Exon 5 of 13	ENSP00000342493.3	Q96TC7-1
RMDN3	ENST00000260385.10	TSL:1	c.770G>C	p.Arg257Pro	missense	Exon 4 of 12	ENSP00000260385.6	Q96TC7-1
RMDN3	ENST00000558777.5	TSL:2	n.*321G>C		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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

249886

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458910

Hom.:

Cov.:

AF XY:

0.00000138

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:

0.0000505

AC:

AN:

39598

South Asian (SAS)

AF:

0.00

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:

0.00

AC:

AN:

1109706

Other (OTH)

AF:

0.00

AC:

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

152236

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41550

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Benign

-0.032

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.78

M_CAP

Benign

0.029

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.6

PhyloP100

0.53

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.19

Sift

Benign

0.055

Sift4G

Benign

0.10

Polyphen

0.95

Vest4

0.76

MVP

0.45

MPC

0.66

ClinPred

0.96

GERP RS

-0.10

PromoterAI

-0.019

Neutral

(source)

Varity_R

0.63

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over