Genetic Variant NM_182577.3:c.611C>T (chr19-464103-G-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_182577.3(CIMAP1D):c.611C>T(p.Pro204Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000134 in 1,339,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CIMAP1D
NM_182577.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.97

Publications

1 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_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.986

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.611C>T	p.Pro204Leu	missense	Exon 4 of 4	NP_872383.1	Q3SX64-1
CIMAP1D	NM_001385597.1		c.503C>T	p.Pro168Leu	missense	Exon 3 of 3	NP_001372526.1	Q3SX64-2
CIMAP1D	NM_001385598.1		c.287C>T	p.Pro96Leu	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.611C>T	p.Pro204Leu	missense	Exon 4 of 4	ENSP00000318029.2	Q3SX64-1
CIMAP1D	ENST00000382696.7	TSL:1	c.503C>T	p.Pro168Leu	missense	Exon 3 of 3	ENSP00000372143.2	Q3SX64-2
CIMAP1D	ENST00000591681.3	TSL:2	n.*64C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000139

AC:

AN:

143826

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:

0.0000154

Gnomad OTH

AF:

0.000497

GnomAD2 exomes

AF:

0.00000793

AC:

AN:

126076

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:

0.00

Gnomad NFE exome

AF:

0.0000209

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000134

AC:

AN:

1195948

Hom.:

Cov.:

AF XY:

0.0000153

AC XY:

AN XY:

587134

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26404

American (AMR)

AF:

0.00

AC:

AN:

26426

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17796

East Asian (EAS)

AF:

0.0000576

AC:

AN:

17376

South Asian (SAS)

AF:

0.00

AC:

AN:

75126

European-Finnish (FIN)

AF:

0.0000370

AC:

AN:

27034

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4164

European-Non Finnish (NFE)

AF:

0.0000115

AC:

AN:

956222

Other (OTH)

AF:

0.0000441

AC:

AN:

45400

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

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:

0.0000139

AC:

AN:

143826

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69876

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

40028

American (AMR)

AF:

0.00

AC:

AN:

14678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3332

East Asian (EAS)

AF:

0.00

AC:

AN:

4294

South Asian (SAS)

AF:

0.00

AC:

AN:

4082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9230

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.0000154

AC:

AN:

64990

Other (OTH)

AF:

0.000497

AC:

AN:

2014

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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:

0.0000189

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

0.27

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

Eigen

Uncertain

0.20

Eigen_PC

Benign

-0.0031

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.86

M_CAP

Pathogenic

0.87

MetaRNN

Pathogenic

0.99

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

3.3

PhyloP100

5.0

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-9.4

REVEL

Pathogenic

0.80

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.033

Polyphen

1.0

Vest4

0.85

MutPred

0.83

Gain of catalytic residue at P204 (P = 0.0467)

MVP

0.83

MPC

0.89

ClinPred

1.0

GERP RS

2.8

Varity_R

0.58

gMVP

0.81

Mutation Taster

=74/26

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

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