Genetic Variant NM_016033.3:c.269C>T (chr8-86488618-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_016033.3(RMDN1):c.269C>T(p.Ala90Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,608,370 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

RMDN1
NM_016033.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.84

Publications

3 publications found

Variant links:

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]

RMDN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RMDN1	NM_016033.3	MANE Select	c.269C>T	p.Ala90Val	missense	Exon 3 of 10	NP_057117.2	Q96DB5-1
RMDN1	NM_001286719.2		c.269C>T	p.Ala90Val	missense	Exon 3 of 9	NP_001273648.1	Q96DB5-2
RMDN1	NM_001286707.2		c.269C>T	p.Ala90Val	missense	Exon 3 of 9	NP_001273636.1	Q96DB5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RMDN1	ENST00000406452.8	TSL:1 MANE Select	c.269C>T	p.Ala90Val	missense	Exon 3 of 10	ENSP00000385927.3	Q96DB5-1
RMDN1	ENST00000902721.1		c.269C>T	p.Ala90Val	missense	Exon 3 of 11	ENSP00000572780.1
RMDN1	ENST00000902719.1		c.311C>T	p.Ala104Val	missense	Exon 3 of 10	ENSP00000572778.1

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000235

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000129

AC:

AN:

247736

AF XY:

0.000127

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:

0.00

Gnomad NFE exome

AF:

0.000284

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000129

AC:

188

AN:

1456264

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

724618

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33232

American (AMR)

AF:

0.00

AC:

AN:

43840

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26000

East Asian (EAS)

AF:

0.00

AC:

AN:

39364

South Asian (SAS)

AF:

0.00

AC:

AN:

85390

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53282

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.000166

AC:

184

AN:

1109262

Other (OTH)

AF:

0.0000499

AC:

AN:

60146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.422

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:

0.000131

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41418

American (AMR)

AF:

0.000131

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

0.000234

Hom.:

Bravo

AF:

0.0000831

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000148

AC:

ClinVar

ClinVar submissions as Germline

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

Uncertain

0.40

BayesDel_addAF

Uncertain

0.079

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-0.69

MutationAssessor

Benign

2.0

PhyloP100

8.8

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.44

Sift

Uncertain

0.026

Sift4G

Benign

0.069

Polyphen

0.97

Vest4

0.92

MVP

0.78

MPC

0.28

ClinPred

0.40

GERP RS

5.7

Varity_R

0.52

gMVP

0.70

Mutation Taster

=22/78

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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