1-145896844-C-T

Variant names:

• chr1-145896844-C-T
• rs150426063
• NM_003637.5:c.2759G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003637.5(ITGA10):​c.2759G>A​(p.Arg920Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R920I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: ITGA10 NM_003637.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.221

Genes affected

ITGA10 (HGNC:6135): (integrin subunit alpha 10) Integrins are integral transmembrane glycoproteins composed of noncovalently linked alpha and beta chains. They participate in cell adhesion as well as cell-surface mediated signalling. This gene encodes an integrin alpha chain and is expressed at high levels in chondrocytes, where it is transcriptionally regulated by AP-2epsilon and Ets-1. The protein encoded by this gene binds to collagen. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035538107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA10	NM_003637.5	c.2759G>A	p.Arg920Lys	missense_variant	Exon 23 of 30	ENST00000369304.8	NP_003628.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA10	ENST00000369304.8	c.2759G>A	p.Arg920Lys	missense_variant	Exon 23 of 30	1	NM_003637.5	ENSP00000358310.3
ITGA10	ENST00000539363.2	c.2330G>A	p.Arg777Lys	missense_variant	Exon 19 of 26	1		ENSP00000439894.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251378 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135860

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461702 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727178

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000720

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 21, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2759G>A (p.R920K) alteration is located in exon 23 (coding exon 23) of the ITGA10 gene. This alteration results from a G to A substitution at nucleotide position 2759, causing the arginine (R) at amino acid position 920 to be replaced by a lysine (K). 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	0.070
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.4
DANN	Benign	0.53
DEOGEN2	Benign	0.040	T;.
LIST_S2	Benign	0.63	T;T
MetaRNN	Benign	0.036	T;T
PROVEAN	Benign	0.040	N;N
Sift	Benign	0.79	T;T
Sift4G	Benign	0.91	T;T
Vest4		0.039
gMVP		0.82

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

LitVar

Other links and lift over

dbSNP: rs150426063; hg19: chr1-145538232;