chr3-124766340-C-G

Position:

• chr3-124766340-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002213.5(ITGB5):​c.2023G>C​(p.Asp675His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITGB5 NM_002213.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.74

Genes affected

ITGB5 (HGNC:6160): (integrin subunit beta 5) This gene encodes a beta subunit of integrin, which can combine with different alpha chains to form a variety of integrin heterodimers. Integrins are integral cell-surface receptors that participate in cell adhesion as well as cell-surface mediated signaling. The alphav beta5 integrin is involved in adhesion to vitronectin. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.806

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB5	NM_002213.5	c.2023G>C	p.Asp675His	missense_variant	13/15	ENST00000296181.9	NP_002204.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB5	ENST00000296181.9	c.2023G>C	p.Asp675His	missense_variant	13/15	1	NM_002213.5	ENSP00000296181.4
ITGB5	ENST00000481591.5	c.1090G>C	p.Asp364His	missense_variant	7/7	5		ENSP00000420814.1
ITGB5	ENST00000460797.5	n.1176G>C		non_coding_transcript_exon_variant	2/4	2
ITGB5	ENST00000461306.1	n.362G>C		non_coding_transcript_exon_variant	4/5	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 20, 2024

The c.2023G>C (p.D675H) alteration is located in exon 13 (coding exon 13) of the ITGB5 gene. This alteration results from a G to C substitution at nucleotide position 2023, causing the aspartic acid (D) at amino acid position 675 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.060	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	0.28	D
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.4	N
REVEL	Pathogenic	0.67
Sift	Benign	0.12	T
Sift4G	Benign	0.088	T
Polyphen		1.0	D
Vest4		0.71
MutPred		0.59		Loss of solvent accessibility (P = 0.0217);
MVP		0.95
MPC		0.89
ClinPred		0.90	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-124485187;