17-8340106-C-T

Variant names:

• chr17-8340106-C-T
• rs1265564094
• NM_153007.5:c.55C>T

Variant summary

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

The NM_153007.5(ODF4):​c.55C>T​(p.Gln19*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,180 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ODF4 NM_153007.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• 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 2 ACMG points.

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

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.55C>T	p.Gln19*	stop_gained	Exon 1 of 3	NP_694552.2	Q2M2E3
	ODF4	NM_001319953.2		c.55C>T	p.Gln19*	stop_gained	Exon 1 of 3	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.55C>T	p.Gln19*	stop_gained	Exon 1 of 3	ENSP00000331086.2	Q2M2E3
	ODF4	ENST00000584943.1	TSL:1	c.55C>T	p.Gln19*	stop_gained	Exon 1 of 3	ENSP00000461942.1	C3TX97
	ODF4	ENST00000636237.1	TSL:5	n.55C>T		non_coding_transcript_exon	Exon 1 of 4	ENSP00000490099.1	A0A1B0GUG5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1385180 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 681246

African (AFR) AF: 0.00 AC: 0 AN: 30872

American (AMR) AF: 0.00 AC: 0 AN: 32504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20692

East Asian (EAS) AF: 0.00 AC: 0 AN: 39136

South Asian (SAS) AF: 0.00 AC: 0 AN: 72450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5378

European-Non Finnish (NFE) AF: 9.29e-7 AC: 1 AN: 1076770

Other (OTH) AF: 0.00 AC: 0 AN: 57088

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	31
DANN	Uncertain	0.99
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.013	N
PhyloP100		0.36
Vest4		0.097
GERP RS		-0.62
PromoterAI		-0.014	Neutral

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

Other links and lift over

dbSNP: rs1265564094; hg19: chr17-8243424;