1-145895337-C-T

Variant names:

• chr1-145895337-C-T
• rs1655231177
• NM_003637.5:c.3171G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP7

The NM_003637.5(ITGA10):​c.3171G>A​(p.Lys1057Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ITGA10 NM_003637.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP7: Synonymous conserved (PhyloP=1.15 with no splicing effect.

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.3171G>A	p.Lys1057Lys	synonymous	Exon 27 of 30	NP_003628.2
	ITGA10	NM_001303040.2		c.2778G>A	p.Lys926Lys	synonymous	Exon 24 of 27	NP_001289969.1
	ITGA10	NM_001303041.2		c.2742G>A	p.Lys914Lys	synonymous	Exon 23 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.3171G>A	p.Lys1057Lys	synonymous	Exon 27 of 30	ENSP00000358310.3	O75578-1
	ITGA10	ENST00000539363.2	TSL:1	c.2742G>A	p.Lys914Lys	synonymous	Exon 23 of 26	ENSP00000439894.1	O75578-3
	ITGA10	ENST00000889441.1		c.3078G>A	p.Lys1026Lys	synonymous	Exon 26 of 29	ENSP00000559500.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461836 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727220

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

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

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60392

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000000666134), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	0.060
CADD	Benign	5.6
DANN	Benign	0.56
PhyloP100		1.1
Mutation Taster		=35/165	disease causing (fs/PTC)

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: rs1655231177; hg19: chr1-145539739;