17-8340389-A-T

Variant names:

• chr17-8340389-A-T
• NM_153007.5:c.338A>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153007.5(ODF4):​c.338A>T​(p.Tyr113Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ODF4 NM_153007.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.275

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05069384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODF4	NM_153007.5	c.338A>T	p.Tyr113Phe	missense_variant	Exon 1 of 3	ENST00000328248.7	NP_694552.2
ODF4	NM_001319953.2	c.109+229A>T		intron_variant	Intron 1 of 2		NP_001306882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODF4	ENST00000328248.7	c.338A>T	p.Tyr113Phe	missense_variant	Exon 1 of 3	1	NM_153007.5	ENSP00000331086.2
ODF4	ENST00000584943.1	c.109+229A>T		intron_variant	Intron 1 of 2	1		ENSP00000461942.1
ODF4	ENST00000636237.1	n.109+229A>T		intron_variant	Intron 1 of 3	5		ENSP00000490099.1
ODF4	ENST00000637186.1	n.-71A>T		upstream_gene_variant		5		ENSP00000490070.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461288 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 726972

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.338A>T (p.Y113F) alteration is located in exon 1 (coding exon 1) of the ODF4 gene. This alteration results from a A to T substitution at nucleotide position 338, causing the tyrosine (Y) at amino acid position 113 to be replaced by a phenylalanine (F). 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	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.5
DANN	Benign	0.94
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.030
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.030	D
Polyphen		0.0010	B
Vest4		0.084
MutPred		0.35		Loss of catalytic residue at P117 (P = 0.0893);
MVP		0.014
MPC		0.64
ClinPred		0.17	T
GERP RS		1.3
Varity_R		0.17
gMVP		0.024

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: chr17-8243707;