Genetic Variant CIMAP1D:p.Pro191Ser (chr19-464143-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_182577.3(CIMAP1D):c.571C>T(p.Pro191Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000037 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CIMAP1D
NM_182577.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.207

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.069346845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIMAP1D	NM_182577.3 link	c.571C>T	p.Pro191Ser	missense_variant	Exon 4 of 4	ENST00000315489.5	NP_872383.1	Q3SX64-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ODF3L2	ENST00000315489.5 link	c.571C>T	p.Pro191Ser	missense_variant	Exon 4 of 4	1	NM_182577.3	ENSP00000318029.2	Q3SX64-1
ODF3L2	ENST00000382696.7 link	c.463C>T	p.Pro155Ser	missense_variant	Exon 3 of 3	1		ENSP00000372143.2	Q3SX64-2
ODF3L2	ENST00000591681.3 link	n.*24C>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

145398

Hom.:

Cov.:

FAILED QC

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:

0.0000457

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

82838

Hom.:

AF XY:

0.0000228

AC XY:

AN XY:

43928

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000328

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000368

AC:

AN:

407984

Hom.:

Cov.:

AF XY:

0.0000323

AC XY:

AN XY:

216946

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000598

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000206

AC:

AN:

145398

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

70690

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000457

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.571C>T (p.P191S) alteration is located in exon 4 (coding exon 4) of the ODF3L2 gene. This alteration results from a C to T substitution at nucleotide position 571, causing the proline (P) at amino acid position 191 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

5.9

DANN

Benign

0.73

DEOGEN2

Benign

0.0046

.;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.069

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

.;L

PrimateAI

Benign

0.47

PROVEAN

Benign

0.080

N;N

REVEL

Benign

0.028

Sift

Benign

0.46

T;T

Sift4G

Benign

0.66

T;T

Polyphen

0.074

B;B

Vest4

0.050

MVP

0.11

MPC

0.27

ClinPred

0.095

GERP RS

3.3

Varity_R

0.036

gMVP

0.30

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over