19-48745473-G-T

Variant names:

• chr19-48745473-G-T
• NM_182575.3:c.235+152C>A

Variant summary

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

The NM_182575.3(IZUMO1):​c.235+152C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000223 in 897,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: IZUMO1 NM_182575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.764

Genes affected

IZUMO1 (HGNC:28539): (izumo sperm-oocyte fusion 1) The sperm-specific protein Izumo, named for a Japanese shrine dedicated to marriage, is essential for sperm-egg plasma membrane binding and fusion (Inoue et al., 2005 [PubMed 15759005]).[supplied by OMIM, Mar 2008]

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 (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IZUMO1	NM_182575.3	c.235+152C>A		intron_variant	Intron 2 of 9	ENST00000332955.7	NP_872381.2
IZUMO1	NM_001321864.1	c.-104-185C>A		intron_variant	Intron 1 of 8		NP_001308793.1
IZUMO1	NM_001321865.1	c.-325+152C>A		intron_variant	Intron 1 of 8		NP_001308794.1
IZUMO1	NR_135832.1	n.242-185C>A		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IZUMO1	ENST00000332955.7	c.235+152C>A		intron_variant	Intron 2 of 9	1	NM_182575.3	ENSP00000327786.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000223 AC: 2 AN: 897598 Hom.: 0 Cov.: 12 AF XY: 0.00000438 AC XY: 2 AN XY: 456152

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: 0.00000309

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.070
DANN	Benign	0.66

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: chr19-49248730;