1-86358810-T-G

Position:

• chr1-86358810-T-G

Variant summary

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

The NM_001366781.1(ODF2L):​c.1249A>C​(p.Thr417Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ODF2L NM_001366781.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.400

Genes affected

ODF2L (HGNC:29225): (outer dense fiber of sperm tails 2 like) Involved in negative regulation of cilium assembly. Located in centriolar satellite and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

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=0.18413875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODF2L	NM_001366781.1	c.1249A>C	p.Thr417Pro	missense_variant	12/17	ENST00000460698.7	NP_001353710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODF2L	ENST00000460698.7	c.1249A>C	p.Thr417Pro	missense_variant	12/17	5	NM_001366781.1	ENSP00000433092.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 20

GnomAD4 genome Cov.: 32

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

Nov 18, 2024

The c.1336A>C (p.T446P) alteration is located in exon 13 (coding exon 12) of the ODF2L gene. This alteration results from a A to C substitution at nucleotide position 1336, causing the threonine (T) at amino acid position 446 to be replaced by a proline (P). 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	0.18
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.024	T;T;.;.;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.59	.;T;T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.0	L;.;.;.;L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.7	N;N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.066	T;T;T;T;T
Sift4G	Benign	0.15	T;T;T;T;T
Polyphen		0.97	D;.;.;P;D
Vest4		0.16
MutPred		0.12		Loss of phosphorylation at T446 (P = 0.0449);.;.;.;Loss of phosphorylation at T446 (P = 0.0449);
MVP		0.62
MPC		0.024
ClinPred		0.54	D
GERP RS		3.2
Varity_R		0.15
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-86824493;