19-2096993-C-T

Variant names:

• chr19-2096993-C-T
• rs761076193
• NM_001039846.2:c.48C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001039846.2(IZUMO4):​c.48C>T​(p.His16His) variant causes a synonymous 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IZUMO4 NM_001039846.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 1 publications found

Genes affected

IZUMO4 (HGNC:26950): (IZUMO family member 4) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-1.39 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039846.2. 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
	IZUMO4	NM_001039846.2	MANE Select	c.48C>T	p.His16His	synonymous	Exon 1 of 10	NP_001034935.1	Q1ZYL8-1
	IZUMO4	NM_001031735.3		c.48C>T	p.His16His	synonymous	Exon 1 of 9	NP_001026905.2	Q1ZYL8-2
	IZUMO4	NM_001363588.2		c.48C>T	p.His16His	synonymous	Exon 1 of 8	NP_001350517.1	A0A0A0MS61

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IZUMO4	ENST00000395301.8	TSL:1 MANE Select	c.48C>T	p.His16His	synonymous	Exon 1 of 10	ENSP00000378712.3	Q1ZYL8-1
	IZUMO4	ENST00000395307.7	TSL:1	c.48C>T	p.His16His	synonymous	Exon 1 of 9	ENSP00000378718.2	Q1ZYL8-2
	IZUMO4	ENST00000395296.5	TSL:2	c.48C>T	p.His16His	synonymous	Exon 1 of 8	ENSP00000378709.2	A0A0A0MS61

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1457870 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725388

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111788

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000660 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.2
DANN	Benign	0.84
PhyloP100		-1.4
PromoterAI		0.060	Neutral

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: rs761076193; hg19: chr19-2096992;