rs1365628587

Variant names:

• chr19-2098091-C-A
• rs1365628587
• NM_001039846.2:c.437C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-2098091-C-A
• chr19-2098091-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039846.2(IZUMO4):​c.437C>A​(p.Thr146Lys) variant causes a missense 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T146I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IZUMO4 NM_001039846.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.991

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21256846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IZUMO4	NM_001039846.2	c.437C>A	p.Thr146Lys	missense_variant	Exon 5 of 10	ENST00000395301.8	NP_001034935.1
IZUMO4	NM_001031735.3	c.437C>A	p.Thr146Lys	missense_variant	Exon 5 of 9		NP_001026905.2
IZUMO4	NM_001363588.2	c.437C>A	p.Thr146Lys	missense_variant	Exon 5 of 8		NP_001350517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IZUMO4	ENST00000395301.8	c.437C>A	p.Thr146Lys	missense_variant	Exon 5 of 10	1	NM_001039846.2	ENSP00000378712.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	0.0044	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.048	T;.;T;.
Eigen	Benign	0.015
Eigen_PC	Benign	0.056
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.7	D;.;.;.
REVEL	Benign	0.18
Sift	Uncertain	0.0020	D;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.73	P;.;.;.
Vest4		0.46
MutPred		0.35		Gain of methylation at T146 (P = 0.0087);Gain of methylation at T146 (P = 0.0087);Gain of methylation at T146 (P = 0.0087);.;
MVP		0.15
MPC		0.16
ClinPred		0.88	D
GERP RS		3.5
Varity_R		0.67
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1365628587; hg19: chr19-2098090;