1-145893560-C-T

Variant names:

• chr1-145893560-C-T
• rs1553743936
• NM_003637.5:c.3304G>A

Variant summary

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

The NM_003637.5(ITGA10):​c.3304G>A​(p.Glu1102Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,840 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ITGA10 NM_003637.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.81
• 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]

ENSG00000244619 (HGNC:58407):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.3304G>A	p.Glu1102Lys	missense	Exon 28 of 30	NP_003628.2
	ITGA10	NM_001303040.2		c.2911G>A	p.Glu971Lys	missense	Exon 25 of 27	NP_001289969.1
	ITGA10	NM_001303041.2		c.2875G>A	p.Glu959Lys	missense	Exon 24 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.3304G>A	p.Glu1102Lys	missense	Exon 28 of 30	ENSP00000358310.3	O75578-1
	ITGA10	ENST00000539363.2	TSL:1	c.2875G>A	p.Glu959Lys	missense	Exon 24 of 26	ENSP00000439894.1	O75578-3
	ITGA10	ENST00000889441.1		c.3211G>A	p.Glu1071Lys	missense	Exon 27 of 29	ENSP00000559500.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459840 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726092

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 85810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53072

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111172

Other (OTH) AF: 0.00 AC: 0 AN: 60314

GnomAD4 genome Cov.: 31

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	0.077
BayesDel_noAF	Pathogenic	0.60
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T
LIST_S2	Uncertain	0.91	D
MetaRNN	Uncertain	0.53	D
PhyloP100		1.8
PROVEAN	Benign	-1.6	N
Sift	Benign	0.078	T
Sift4G	Benign	0.16	T
Vest4		0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.91

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: rs1553743936; hg19: chr1-145541516;