NM_153007.5:c.55C>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153007.5(ODF4):​c.55C>A​(p.Gln19Lys) variant causes a missense 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. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ODF4 NM_153007.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054409444).

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>A	p.Gln19Lys	missense	Exon 1 of 3	NP_694552.2	Q2M2E3
	ODF4	NM_001319953.2		c.55C>A	p.Gln19Lys	missense	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>A	p.Gln19Lys	missense	Exon 1 of 3	ENSP00000331086.2	Q2M2E3
	ODF4	ENST00000584943.1	TSL:1	c.55C>A	p.Gln19Lys	missense	Exon 1 of 3	ENSP00000461942.1	C3TX97
	ODF4	ENST00000636237.1	TSL:5	n.55C>A		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: 0.00000147 AC XY: 1 AN XY: 681246

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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

American (AMR) AF: 0.0000308 AC: 1 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: 0.00 AC: 0 AN: 1076770

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

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	0.086
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.4
DANN	Benign	0.67
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0099	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.36
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.038
Sift	Benign	0.41	T
Sift4G	Benign	0.071	T
Polyphen		0.0090	B
Vest4		0.050
MutPred		0.064		Gain of ubiquitination at Q19 (P = 0.0085)
MVP		0.014
MPC		0.32
ClinPred		0.067	T
GERP RS		-0.62
PromoterAI		-0.0083	Neutral
Varity_R		0.072
gMVP		0.086

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

dbSNP: rs1265564094; hg19: chr17-8243424;