1-145895337-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003637.5(ITGA10):​c.3171G>T​(p.Lys1057Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGA10 NM_003637.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.124518365).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA10	NM_003637.5	c.3171G>T	p.Lys1057Asn	missense_variant	Exon 27 of 30	ENST00000369304.8	NP_003628.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA10	ENST00000369304.8	c.3171G>T	p.Lys1057Asn	missense_variant	Exon 27 of 30	1	NM_003637.5	ENSP00000358310.3
ITGA10	ENST00000539363.2	c.2742G>T	p.Lys914Asn	missense_variant	Exon 23 of 26	1		ENSP00000439894.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3171G>T (p.K1057N) alteration is located in exon 27 (coding exon 27) of the ITGA10 gene. This alteration results from a G to T substitution at nucleotide position 3171, causing the lysine (K) at amino acid position 1057 to be replaced by an asparagine (N). 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	Uncertain	0.42
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Benign	0.63
DEOGEN2	Benign	0.083	T;.
LIST_S2	Benign	0.84	T;T
MetaRNN	Benign	0.12	T;T
PROVEAN	Benign	-0.33	N;N
Sift	Benign	0.92	T;T
Sift4G	Benign	0.49	T;T
Vest4		0.24
gMVP		0.93

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1655231177; hg19: chr1-145539739;