Variant 19-48745630-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_182575.3(IZUMO1):c.230T>C(p.Val77Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,612,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

IZUMO1
NM_182575.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.292

Variant links:

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]

IZUMO1 links:

IZUMO1 (HGNC:):

IZUMO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06075722).

BP6

Variant 19-48745630-A-G is Benign according to our data. Variant chr19-48745630-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2457111.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IZUMO1	NM_182575.3 linkuse as main transcript	c.230T>C	p.Val77Ala	missense_variant	2/10	ENST00000332955.7	NP_872381.2	Q8IYV9-1
IZUMO1	NM_001321865.1 linkuse as main transcript	c.-330T>C		5_prime_UTR_variant	1/9		NP_001308794.1	Q8IYV9
IZUMO1	NM_001321864.1 linkuse as main transcript	c.-104-342T>C		intron_variant			NP_001308793.1
IZUMO1	NR_135832.1 linkuse as main transcript	n.241+62T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IZUMO1	ENST00000332955.7 linkuse as main transcript	c.230T>C	p.Val77Ala	missense_variant	2/10	1	NM_182575.3	ENSP00000327786.2		Q8IYV9-1

Frequencies

GnomAD3 genomes

AF:

0.000139

AC:

AN:

150864

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000734

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000251

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.0000678

AC:

AN:

250874

Hom.:

AF XY:

0.0000590

AC XY:

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000154

AC:

225

AN:

1461878

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

109

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

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:

0.000188

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000139

AC:

AN:

150864

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

73632

show subpopulations

Gnomad4 AFR

AF:

0.0000734

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000251

Gnomad4 OTH

AF:

0.000481

Alfa

AF:

0.000223

Hom.:

Bravo

AF:

0.000128

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 13, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.7

DANN

Benign

0.64

DEOGEN2

Benign

0.29

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.53

M_CAP

Benign

0.0049

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.16

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.6

REVEL

Benign

0.014

Sift

Benign

0.24

Sift4G

Benign

0.17

Polyphen

0.071

Vest4

0.14

MVP

0.030

MPC

0.61

ClinPred

0.017

GERP RS

-2.5

Varity_R

0.23

gMVP

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over