1-145892846-A-C

Variant names:

• chr1-145892846-A-C
• rs375285555
• NM_003637.5:c.3456T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003637.5(ITGA10):​c.3456T>G​(p.His1152Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: ITGA10 NM_003637.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.147
• Publications: 1 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]

ENSG00000244619 (HGNC:58407):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13028589).

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.3456T>G	p.His1152Gln	missense	Exon 30 of 30	NP_003628.2
	ITGA10	NM_001303040.2		c.3063T>G	p.His1021Gln	missense	Exon 27 of 27	NP_001289969.1
	ITGA10	NM_001303041.2		c.3027T>G	p.His1009Gln	missense	Exon 26 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.3456T>G	p.His1152Gln	missense	Exon 30 of 30	ENSP00000358310.3	O75578-1
	ITGA10	ENST00000539363.2	TSL:1	c.3027T>G	p.His1009Gln	missense	Exon 26 of 26	ENSP00000439894.1	O75578-3
	ITGA10	ENST00000889441.1		c.3363T>G	p.His1121Gln	missense	Exon 29 of 29	ENSP00000559500.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152096 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251208 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.0000578

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: 0.000163

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1461548 Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9 AN XY: 727110

African (AFR) AF: 0.000597 AC: 20 AN: 33474

American (AMR) AF: 0.0000671 AC: 3 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111710

Other (OTH) AF: 0.0000166 AC: 1 AN: 60388

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152096 Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4 AN XY: 74290

African (AFR) AF: 0.000314 AC: 13 AN: 41414

American (AMR) AF: 0.000197 AC: 3 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000134 Hom.: 0

Bravo AF: 0.000159

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	0.076
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.092	T
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.13	T
PhyloP100		-0.15
PROVEAN	Benign	0.44	N
Sift	Benign	0.12	T
Sift4G	Benign	0.071	T
Vest4		0.24
gMVP		0.85

Splicing

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

Other links and lift over

dbSNP: rs375285555; hg19: chr1-145542230;