19-48743609-A-T

Position:

• chr19-48743609-A-T

Variant summary

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

The NM_182575.3(IZUMO1):​c.419-84T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000225 in 889,524 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: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: IZUMO1 NM_182575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

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=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IZUMO1	NM_182575.3	c.419-84T>A		intron_variant		ENST00000332955.7
IZUMO1	NM_001321864.1	c.80-84T>A		intron_variant
IZUMO1	NM_001321865.1	c.-141-84T>A		intron_variant
IZUMO1	NR_135832.1	n.425-84T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IZUMO1	ENST00000332955.7	c.419-84T>A		intron_variant		1	NM_182575.3	P1
IZUMO1	ENST00000595517.5	c.*145-84T>A		intron_variant, NMD_transcript_variant		1
IZUMO1	ENST00000595937.5	c.419-84T>A		intron_variant, NMD_transcript_variant		1
IZUMO1	ENST00000597553.1	n.1641T>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000225 AC: 2 AN: 889524 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 463240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000277

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000167

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.74

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

LitVar

Other links and lift over

dbSNP: rs838147; hg19: chr19-49246866;