chr19-48743609-A-C

Variant names:

• chr19-48743609-A-C
• rs838147
• NM_182575.3:c.419-84T>G

Variant summary

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

The NM_182575.3(IZUMO1):​c.419-84T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: IZUMO1 NM_182575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323
• Publications: 43 publications found

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

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 (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182575.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IZUMO1	NM_182575.3	MANE Select	c.419-84T>G		intron	N/A	NP_872381.2
	IZUMO1	NM_001321864.1		c.80-84T>G		intron	N/A	NP_001308793.1
	IZUMO1	NM_001321865.1		c.-141-84T>G		intron	N/A	NP_001308794.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IZUMO1	ENST00000332955.7	TSL:1 MANE Select	c.419-84T>G		intron	N/A	ENSP00000327786.2
	IZUMO1	ENST00000595517.5	TSL:1	n.*145-84T>G		intron	N/A	ENSP00000471815.1
	IZUMO1	ENST00000595937.5	TSL:1	n.419-84T>G		intron	N/A	ENSP00000470144.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 12

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 13259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.67
PhyloP100		-0.32

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: rs838147; hg19: chr19-49246866;