chr19-464145-G-A

Position:

• chr19-464145-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182577.3(CIMAP1D):​c.569C>T​(p.Pro190Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 536,066 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: CIMAP1D NM_182577.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.17

Genes affected

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

ODF3L2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10977733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIMAP1D	NM_182577.3	c.569C>T	p.Pro190Leu	missense_variant	4/4	ENST00000315489.5	NP_872383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODF3L2	ENST00000315489.5	c.569C>T	p.Pro190Leu	missense_variant	4/4	1	NM_182577.3	ENSP00000318029.2
ODF3L2	ENST00000382696.7	c.461C>T	p.Pro154Leu	missense_variant	3/3	1		ENSP00000372143.2
ODF3L2	ENST00000591681.3	n.*22C>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000187 AC: 1 AN: 536066 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 279196

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: 0.00000281

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.569C>T (p.P190L) 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 569, causing the proline (P) at amino acid position 190 to be replaced by a leucine (L). 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	0.075
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.77
DEOGEN2	Benign	0.011	.;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	.;L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.021
Sift	Benign	0.23	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.77	P;B
Vest4		0.28
MutPred		0.24		.;Loss of glycosylation at P190 (P = 0.021);
MVP		0.31
MPC		0.27
ClinPred		0.40	T
GERP RS		2.7
Varity_R		0.051
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-464145;