chr3-37471057-A-T

Variant names:

• chr3-37471057-A-T
• rs774223835
• NM_002207.3:c.236A>T

Variant summary

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

The NM_002207.3(ITGA9):​c.236A>T​(p.Lys79Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K79T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ITGA9 NM_002207.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06
• Publications: 1 publications found

Genes affected

ITGA9 (HGNC:6145): (integrin subunit alpha 9) This gene encodes an alpha integrin. Integrins are heterodimeric integral membrane glycoproteins composed of an alpha chain and a beta chain that mediate cell-cell and cell-matrix adhesion. The protein encoded by this gene, when bound to the beta 1 chain, forms an integrin that is a receptor for VCAM1, cytotactin and osteopontin. Expression of this gene has been found to be upregulated in small cell lung cancers. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.17496088).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002207.3. 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
	ITGA9	NM_002207.3	MANE Select	c.236A>T	p.Lys79Met	missense	Exon 2 of 28	NP_002198.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA9	ENST00000264741.10	TSL:1 MANE Select	c.236A>T	p.Lys79Met	missense	Exon 2 of 28	ENSP00000264741.5	Q13797
	ITGA9	ENST00000422441.5	TSL:1	c.236A>T	p.Lys79Met	missense	Exon 2 of 16	ENSP00000397258.1	E9PDS3
	ITGA9	ENST00000921363.1		c.236A>T	p.Lys79Met	missense	Exon 2 of 28	ENSP00000591422.1

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152072 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000852

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: 0.0000119 AC: 3 AN: 251472 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

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: 1461806 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727204

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44722

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: 53412

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111940

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152072 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74272

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.000852 AC: 13 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.0081
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.085
Sift	Benign	0.10	T
Sift4G	Benign	0.11	T
Polyphen		0.85	P
Vest4		0.47
MutPred		0.37		Loss of methylation at K79 (P = 0.006)
MVP		0.54
MPC		0.48
ClinPred		0.36	T
GERP RS		3.0
Varity_R		0.070
gMVP		0.57
Mutation Taster		=84/16	polymorphism

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: rs774223835; hg19: chr3-37512548;