Genetic Variant CIMAP1D:p.Arg216His (chr19-464067-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_182577.3(CIMAP1D):c.647G>A(p.Arg216His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,561,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R216C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

CIMAP1D
NM_182577.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.624

Publications

0 publications found

Variant links:

Genes affected

CIMAP1D (HGNC:26841): (CIMAP1 family member D) Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

CIMAP1D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.068692386).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182577.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CIMAP1D	NM_182577.3	MANE Select	c.647G>A	p.Arg216His	missense	Exon 4 of 4	NP_872383.1	Q3SX64-1
CIMAP1D	NM_001385597.1		c.539G>A	p.Arg180His	missense	Exon 3 of 3	NP_001372526.1	Q3SX64-2
CIMAP1D	NM_001385598.1		c.323G>A	p.Arg108His	missense	Exon 4 of 4	NP_001372527.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CIMAP1D	ENST00000315489.5	TSL:1 MANE Select	c.647G>A	p.Arg216His	missense	Exon 4 of 4	ENSP00000318029.2	Q3SX64-1
CIMAP1D	ENST00000382696.7	TSL:1	c.539G>A	p.Arg180His	missense	Exon 3 of 3	ENSP00000372143.2	Q3SX64-2
CIMAP1D	ENST00000591681.3	TSL:2	n.*100G>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000363

AC:

AN:

137596

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:

0.0000752

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000553

AC:

AN:

180988

AF XY:

0.0000507

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:

0.000119

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000119

AC:

170

AN:

1423986

Hom.:

Cov.:

AF XY:

0.0000992

AC XY:

AN XY:

705536

show subpopulations

African (AFR)

AF:

0.0000305

AC:

AN:

32750

American (AMR)

AF:

0.0000257

AC:

AN:

38844

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25364

East Asian (EAS)

AF:

0.00

AC:

AN:

37578

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82442

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5422

European-Non Finnish (NFE)

AF:

0.000149

AC:

163

AN:

1094520

Other (OTH)

AF:

0.0000679

AC:

AN:

58938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

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:

0.0000363

AC:

AN:

137596

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

65486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

36152

American (AMR)

AF:

0.00

AC:

AN:

11694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

4566

South Asian (SAS)

AF:

0.00

AC:

AN:

4418

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7784

Middle Eastern (MID)

AF:

0.00

AC:

AN:

250

European-Non Finnish (NFE)

AF:

0.0000752

AC:

AN:

66512

Other (OTH)

AF:

0.00

AC:

AN:

1874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.000126

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000347

AC:

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

0.097

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.84

M_CAP

Benign

0.026

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.62

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.024

Sift

Benign

0.088

Sift4G

Benign

0.067

Polyphen

0.24

Vest4

0.21

MutPred

0.40

Loss of MoRF binding (P = 0.0279)

MVP

0.14

MPC

0.85

ClinPred

0.14

GERP RS

1.4

Varity_R

0.088

gMVP

0.38

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over