22-50531768-C-T

Variant names:

• chr22-50531768-C-T
• rs1399626307
• NM_001014440.4:c.115G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001014440.4(CIMAP1B):​c.115G>A​(p.Ala39Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,214,816 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: CIMAP1B NM_001014440.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.915

Genes affected

CIMAP1B (HGNC:34388): (ciliary microtubule associated protein 1B) Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.021889031).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIMAP1B	NM_001014440.4	c.115G>A	p.Ala39Thr	missense_variant	Exon 3 of 7	ENST00000329363.9	NP_001014440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODF3B	ENST00000329363.9	c.115G>A	p.Ala39Thr	missense_variant	Exon 3 of 7	5	NM_001014440.4	ENSP00000382804.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000165 AC: 2 AN: 1214816 Hom.: 0 Cov.: 32 AF XY: 0.00000171 AC XY: 1 AN XY: 586504

Gnomad4 AFR exome AF: 0.0000424

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000366

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.115G>A (p.A39T) alteration is located in exon 3 (coding exon 2) of the ODF3B gene. This alteration results from a G to A substitution at nucleotide position 115, causing the alanine (A) at amino acid position 39 to be replaced by a threonine (T). 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	0.067
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.11
DANN	Benign	0.95
DEOGEN2	Benign	0.00097	T;T;T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0052	N
LIST_S2	Benign	0.13	T;T;.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.022	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.26	N;.;N;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.16	N;N;N;N
REVEL	Benign	0.0040
Sift	Benign	0.62	T;T;T;T
Sift4G	Benign	0.60	T;T;T;T
Polyphen		0.010	B;.;B;.
Vest4		0.046
MutPred		0.22		Gain of glycosylation at A39 (P = 0.0105);Gain of glycosylation at A39 (P = 0.0105);Gain of glycosylation at A39 (P = 0.0105);Gain of glycosylation at A39 (P = 0.0105);
MVP		0.040
MPC		1.6
ClinPred		0.043	T
GERP RS		-4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.037
gMVP		0.086

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

LitVar

Other links and lift over

dbSNP: rs1399626307; hg19: chr22-50970197;