11-198543-G-C

Position:

• chr11-198543-G-C

Variant summary

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

The NM_053280.5(CIMAP1A):​c.492G>C​(p.Lys164Asn) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CIMAP1A NM_053280.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.722

Genes affected

CIMAP1A (HGNC:19905): (ciliary microtubule associated protein 1A) ODF3 is a component of sperm flagella outer dense fibers, which add stiffness, elastic recoil, and protection against shearing forces during sperm movement.[supplied by OMIM, Apr 2004]

BET1L (HGNC:19348): (Bet1 golgi vesicular membrane trafficking protein like) Enables SNAP receptor activity. Involved in regulation of retrograde vesicle-mediated transport, Golgi to ER and retrograde transport, endosome to Golgi. Located in Golgi apparatus and endosome. Implicated in uterine fibroid. Biomarker of endometrial adenocarcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ODF3 (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=0.16853857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIMAP1A	NM_053280.5	c.492G>C	p.Lys164Asn	missense_variant	5/7	ENST00000325113.9	NP_444510.2
CIMAP1A	NM_001286136.2	c.492G>C	p.Lys164Asn	missense_variant	5/6		NP_001273065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODF3	ENST00000325113.9	c.492G>C	p.Lys164Asn	missense_variant	5/7	1	NM_053280.5	ENSP00000325868.5
ODF3	ENST00000525282.1	c.492G>C	p.Lys164Asn	missense_variant	5/6	1		ENSP00000436588.1
BET1L	ENST00000410108.5	c.168+7068C>G		intron_variant		3		ENSP00000386558.1
ODF3	ENST00000531679.1	n.1335G>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

Aug 20, 2024

The c.492G>C (p.K164N) alteration is located in exon 5 (coding exon 4) of the ODF3 gene. This alteration results from a G to C substitution at nucleotide position 492, causing the lysine (K) at amino acid position 164 to be replaced by an asparagine (N). 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	Uncertain	0.47
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0087	T;.;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.83	T;D;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.40	N;N;.
REVEL	Benign	0.022
Sift	Benign	0.41	T;T;.
Sift4G	Benign	0.40	T;T;T
Polyphen		0.55	P;.;.
Vest4		0.51
MutPred		0.32		Loss of MoRF binding (P = 0.0402);Loss of MoRF binding (P = 0.0402);.;
MVP		0.12
MPC		0.40
ClinPred		0.38	T
GERP RS		1.2
Varity_R		0.066
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr11-198543;