1-145897544-T-C

Variant names:

• chr1-145897544-T-C
• rs1282023645
• NM_003637.5:c.2542A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003637.5(ITGA10):​c.2542A>G​(p.Arg848Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ITGA10 NM_003637.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.07
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18394303).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003637.5. 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
	ITGA10	NM_003637.5	MANE Select	c.2542A>G	p.Arg848Gly	missense	Exon 20 of 30	NP_003628.2
	ITGA10	NM_001303040.2		c.2149A>G	p.Arg717Gly	missense	Exon 17 of 27	NP_001289969.1
	ITGA10	NM_001303041.2		c.2113A>G	p.Arg705Gly	missense	Exon 16 of 26	NP_001289970.1	O75578-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA10	ENST00000369304.8	TSL:1 MANE Select	c.2542A>G	p.Arg848Gly	missense	Exon 20 of 30	ENSP00000358310.3	O75578-1
	ITGA10	ENST00000539363.2	TSL:1	c.2113A>G	p.Arg705Gly	missense	Exon 16 of 26	ENSP00000439894.1	O75578-3
	ITGA10	ENST00000889441.1		c.2542A>G	p.Arg848Gly	missense	Exon 20 of 29	ENSP00000559500.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 250956 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.067	T
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.18	T
PhyloP100		1.1
PROVEAN	Benign	-0.89	N
Sift	Benign	0.16	T
Sift4G	Benign	0.34	T
Vest4		0.18
gMVP		0.97

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1282023645; hg19: chr1-145537532;