19-48741930-T-A

Variant names:

• chr19-48741930-T-A
• rs1413665506
• NM_182575.3:c.613A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182575.3(IZUMO1):​c.613A>T​(p.Asn205Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IZUMO1 NM_182575.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.576
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25877795).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IZUMO1	NM_182575.3	MANE Select	c.613A>T	p.Asn205Tyr	missense	Exon 8 of 10	NP_872381.2	Q8IYV9-1
	IZUMO1	NM_001321864.1		c.274A>T	p.Asn92Tyr	missense	Exon 7 of 9	NP_001308793.1
	IZUMO1	NM_001321865.1		c.91A>T	p.Asn31Tyr	missense	Exon 7 of 9	NP_001308794.1	Q8IYV9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IZUMO1	ENST00000332955.7	TSL:1 MANE Select	c.613A>T	p.Asn205Tyr	missense	Exon 8 of 10	ENSP00000327786.2	Q8IYV9-1
	IZUMO1	ENST00000595517.5	TSL:1	n.*369A>T		non_coding_transcript_exon	Exon 7 of 9	ENSP00000471815.1	Q8IYV9-3
	IZUMO1	ENST00000595937.5	TSL:1	n.*65A>T		non_coding_transcript_exon	Exon 7 of 9	ENSP00000470144.1	Q8IYV9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 244214 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451612 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 720734

African (AFR) AF: 0.00 AC: 0 AN: 33172

American (AMR) AF: 0.00 AC: 0 AN: 43594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25724

East Asian (EAS) AF: 0.00 AC: 0 AN: 39458

South Asian (SAS) AF: 0.00 AC: 0 AN: 85540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53264

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5738

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105292

Other (OTH) AF: 0.00 AC: 0 AN: 59830

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.58
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.24
Sift	Benign	0.15	T
Sift4G	Uncertain	0.014	D
Polyphen		0.96	D
Vest4		0.28
MutPred		0.29		Loss of disorder (P = 0.0781)
MVP		0.93
MPC		1.3
ClinPred		0.77	D
GERP RS		1.8
Varity_R		0.13
gMVP		0.42
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1413665506; hg19: chr19-49245187;