15-75727454-G-A

Position:

• chr15-75727454-G-A

Variant summary

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

The ENST00000332145.3(CIMAP1C):​c.739G>A​(p.Val247Met) 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: CIMAP1C ENST00000332145.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.674

Genes affected

ODF3L1 (HGNC:):

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 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=0.09586191).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODF3L1	NM_175881.5	c.739G>A	p.Val247Met	missense_variant	4/4	ENST00000332145.3	NP_787077.1
ODF3L1	XM_006720414.4	c.790G>A	p.Val264Met	missense_variant	4/4		XP_006720477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIMAP1C	ENST00000332145.3	c.739G>A	p.Val247Met	missense_variant	4/4	1	NM_175881.5	ENSP00000329584	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Mar 03, 2022

The c.739G>A (p.V247M) alteration is located in exon 4 (coding exon 4) of the ODF3L1 gene. This alteration results from a G to A substitution at nucleotide position 739, causing the valine (V) at amino acid position 247 to be replaced by a methionine (M). 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	0.086
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.11
Sift	Uncertain	0.024	D
Sift4G	Benign	0.29	T
Polyphen		0.85	P
Vest4		0.13
MutPred		0.54		Gain of ubiquitination at K249 (P = 0.0898);
MVP		0.014
MPC		0.31
ClinPred		0.58	D
GERP RS		-0.30
Varity_R		0.12
gMVP		0.32

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: chr15-76019795;