17-8340269-C-A

Variant names:

• chr17-8340269-C-A
• NM_153007.5:c.218C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153007.5(ODF4):​c.218C>A​(p.Thr73Lys) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ODF4 NM_153007.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0850
• Publications: 0 publications found

Genes affected

ODF4 (HGNC:19056): (outer dense fiber of sperm tails 4) This gene encodes a protein that is localized in the outer dense fibers of the tails of mature sperm. This protein is thought to have some important role in the sperm tail. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ODF4 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0952155).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153007.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODF4	NM_153007.5	MANE Select	c.218C>A	p.Thr73Lys	missense	Exon 1 of 3	NP_694552.2	Q2M2E3
	ODF4	NM_001319953.2		c.109+109C>A		intron	N/A	NP_001306882.1	C3TX97

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODF4	ENST00000328248.7	TSL:1 MANE Select	c.218C>A	p.Thr73Lys	missense	Exon 1 of 3	ENSP00000331086.2	Q2M2E3
	ODF4	ENST00000584943.1	TSL:1	c.109+109C>A		intron	N/A	ENSP00000461942.1	C3TX97
	ODF4	ENST00000636237.1	TSL:5	n.109+109C>A		intron	N/A	ENSP00000490099.1	A0A1B0GUG5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	2.9
DANN	Benign	0.75
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.085
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.030
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.011	D
Polyphen		0.40	B
Vest4		0.22
MutPred		0.40		Gain of methylation at T73 (P = 0.0189)
MVP		0.030
MPC		0.25
ClinPred		0.45	T
GERP RS		0.27
PromoterAI		-0.014	Neutral
Varity_R		0.15
gMVP		0.19

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

Other links and lift over

hg19: chr17-8243587;