16-31261765-C-G

Variant names:

• chr16-31261765-C-G
• rs535986528
• NM_000632.4:c.102C>G

Variant summary

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

The NM_000632.4(ITGAM):​c.102C>G​(p.Phe34Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F34F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 29)
• Consequence: ITGAM NM_000632.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 1 publications found

Genes affected

ITGAM (HGNC:6149): (integrin subunit alpha M) This gene encodes the integrin alpha M chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This I-domain containing alpha integrin combines with the beta 2 chain (ITGB2) to form a leukocyte-specific integrin referred to as macrophage receptor 1 ('Mac-1'), or inactivated-C3b (iC3b) receptor 3 ('CR3'). The alpha M beta 2 integrin is important in the adherence of neutrophils and monocytes to stimulated endothelium, and also in the phagocytosis of complement coated particles. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ITGAM Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

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_000632.4. 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
	ITGAM	NM_000632.4	MANE Select	c.102C>G	p.Phe34Leu	missense	Exon 2 of 30	NP_000623.2	P11215-1
	ITGAM	NM_001145808.2		c.102C>G	p.Phe34Leu	missense	Exon 2 of 30	NP_001139280.1	P11215-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAM	ENST00000544665.9	TSL:1 MANE Select	c.102C>G	p.Phe34Leu	missense	Exon 2 of 30	ENSP00000441691.3	P11215-1
	ITGAM	ENST00000943361.1		c.102C>G	p.Phe34Leu	missense	Exon 2 of 30	ENSP00000613420.1
	ITGAM	ENST00000648685.1		c.102C>G	p.Phe34Leu	missense	Exon 2 of 30	ENSP00000496959.1	P11215-2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247812 AF XY: 0.00000744

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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 Cov.: 30

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	4.9
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.58	D
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.063	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.084	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Uncertain	0.086	D
MutationAssessor	Pathogenic	3.4	M
PhyloP100		-2.3
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.62		Loss of helix (P = 0.079)
MVP		0.86
MPC		1.1
ClinPred		0.94	D
GERP RS		-4.5
Varity_R		0.46
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs535986528; hg19: chr16-31273086;