NM_000889.3:c.2284G>A

Variant names:

• chr12-53191891-C-T
• rs543658428
• NM_000889.3:c.2284G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000889.3(ITGB7):​c.2284G>A​(p.Glu762Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. E762Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGB7 NM_000889.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.78
• Publications: 0 publications found

Genes affected

ITGB7 (HGNC:6162): (integrin subunit beta 7) This gene encodes a protein that is a member of the integrin superfamily. Members of this family are adhesion receptors that function in signaling from the extracellular matrix to the cell. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. The encoded protein forms dimers with an alpha4 chain or an alphaE chain and plays a role in leukocyte adhesion. Dimerization with alpha4 forms a homing receptor for migration of lymphocytes to the intestinal mucosa and Peyer's patches. Dimerization with alphaE permits binding to the ligand epithelial cadherin, a calcium-dependent adhesion molecule. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Sep 2013]

ZNF740 (HGNC:27465): (zinc finger protein 740) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.922

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB7	NM_000889.3	c.2284G>A	p.Glu762Lys	missense_variant	Exon 15 of 16	ENST00000267082.10	NP_000880.1
ZNF740	NM_001004304.4	c.*4301C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000416904.5	NP_001004304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB7	ENST00000267082.10	c.2284G>A	p.Glu762Lys	missense_variant	Exon 15 of 16	1	NM_000889.3	ENSP00000267082.4
ZNF740	ENST00000416904.5	c.*4301C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_001004304.4	ENSP00000409463.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.84	D;D;.
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	.;D;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.92	D;D;D
MetaSVM	Uncertain	0.63	D
MutationAssessor	Uncertain	2.4	M;M;.
PhyloP100		3.8
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.5	D;D;.
REVEL	Pathogenic	0.80
Sift	Uncertain	0.0010	D;D;.
Sift4G	Uncertain	0.032	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.68
MutPred		0.77		Gain of methylation at E762 (P = 0.0021);Gain of methylation at E762 (P = 0.0021);.;
MVP		0.96
MPC		1.0
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.70
gMVP		0.63
Mutation Taster		=75/25	polymorphism

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: rs543658428; hg19: chr12-53585675;