chr11-199999-A-G

Position:

• chr11-199999-A-G

Variant summary

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

The NM_053280.5(ODF3):​c.731A>G​(p.Asp244Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ODF3 NM_053280.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21

Genes affected

ODF3 (HGNC:):

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODF3	NM_053280.5	c.731A>G	p.Asp244Gly	missense_variant	7/7	ENST00000325113.9
ODF3	NM_001286136.2	c.590A>G	p.Asp197Gly	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIMAP1A	ENST00000325113.9	c.731A>G	p.Asp244Gly	missense_variant	7/7	1	NM_053280.5	P1
CIMAP1A	ENST00000525282.1	c.590A>G	p.Asp197Gly	missense_variant	6/6	1
BET1L	ENST00000410108.5	c.168+5612T>C		intron_variant		3
CIMAP1A	ENST00000531679.1	n.2791A>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

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 16, 2022

The c.731A>G (p.D244G) alteration is located in exon 7 (coding exon 6) of the ODF3 gene. This alteration results from a A to G substitution at nucleotide position 731, causing the aspartic acid (D) at amino acid position 244 to be replaced by a glycine (G). 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	0.30
BayesDel_addAF	Uncertain	0.069	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T;.;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.85	D;T;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	2.0	M;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.5	D;D;.
REVEL	Benign	0.22
Sift	Uncertain	0.0040	D;D;.
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.48
MutPred		0.41		Gain of glycosylation at S243 (P = 0.1014);.;.;
MVP		0.38
MPC		0.61
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.50
gMVP		0.62

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: chr11-199999;