rs369506738

Variant names:

• chr17-8345346-C-G
• NM_153007.5:c.458C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-8345346-C-G
• chr17-8345346-C-T

Variant summary

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

The NM_153007.5(ODF4):​c.458C>G​(p.Thr153Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T153I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ODF4 NM_153007.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457

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 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 rank	MANE	Protein	UniProt
ODF4	NM_153007.5	c.458C>G	p.Thr153Ser	missense_variant	Exon 2 of 3	ENST00000328248.7	NP_694552.2
ODF4	NM_001319953.2	c.113C>G	p.Thr38Ser	missense_variant	Exon 2 of 3		NP_001306882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODF4	ENST00000328248.7	c.458C>G	p.Thr153Ser	missense_variant	Exon 2 of 3	1	NM_153007.5	ENSP00000331086.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461248 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726964

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.0
DANN	Benign	0.27
DEOGEN2	Benign	0.028	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.25	T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.046	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.9	N;.
REVEL	Benign	0.037
Sift	Benign	0.71	T;.
Sift4G	Benign	0.16	T;T
Polyphen		0.046	B;.
Vest4		0.16
MutPred		0.28		Gain of disorder (P = 0.0433);.;
MVP		0.014
MPC		0.20
ClinPred		0.031	T
GERP RS		-5.6
Varity_R		0.046
gMVP		0.061

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.38		Position offset: 1

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: chr17-8248664;