chr15-75724240-C-A

Position:

• chr15-75724240-C-A

Variant summary

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

The NM_175881.5(CIMAP1C):​c.41C>A​(p.Ala14Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,804 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: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CIMAP1C NM_175881.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0400

Genes affected

CIMAP1C (HGNC:28735): (ciliary microtubule associated protein 1C) 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=0.054214835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIMAP1C	NM_175881.5	c.41C>A	p.Ala14Glu	missense_variant	1/4	ENST00000332145.3	NP_787077.1
CIMAP1C	XM_006720414.4	c.41C>A	p.Ala14Glu	missense_variant	1/4		XP_006720477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODF3L1	ENST00000332145.3	c.41C>A	p.Ala14Glu	missense_variant	1/4	1	NM_175881.5	ENSP00000329584.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461804 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Jun 22, 2023

The c.41C>A (p.A14E) alteration is located in exon 1 (coding exon 1) of the ODF3L1 gene. This alteration results from a C to A substitution at nucleotide position 41, causing the alanine (A) at amino acid position 14 to be replaced by a glutamic acid (E). 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	0.16
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.0
DANN	Benign	0.61
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.030
Sift	Benign	0.046	D
Sift4G	Uncertain	0.046	D
Polyphen		0.18	B
Vest4		0.13
MutPred		0.14		Gain of catalytic residue at A14 (P = 0.0419);
MVP		0.014
MPC		0.33
ClinPred		0.064	T
GERP RS		-1.6
Varity_R		0.085
gMVP		0.39

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: rs1327865069; hg19: chr15-76016581;