NM_000632.4:c.111C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000632.4(ITGAM):​c.111C>A​(p.Ser37Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S37S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 29)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ITGAM
NM_000632.4 missense

Scores

1
6
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.81
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37180513).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ITGAMNM_000632.4 linkc.111C>A p.Ser37Arg missense_variant Exon 2 of 30 ENST00000544665.9 NP_000623.2 P11215-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ITGAMENST00000544665.9 linkc.111C>A p.Ser37Arg missense_variant Exon 2 of 30 1 NM_000632.4 ENSP00000441691.3 P11215-1
ITGAMENST00000648685.1 linkc.111C>A p.Ser37Arg missense_variant Exon 2 of 30 ENSP00000496959.1 P11215-2

Frequencies

GnomAD3 genomes
Cov.:
29
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1460516
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726484
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.62
BayesDel_addAF
Benign
-0.034
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
7.0
DANN
Uncertain
0.99
DEOGEN2
Benign
0.36
.;.;T
Eigen
Benign
-0.84
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.043
N
LIST_S2
Benign
0.79
.;T;T
M_CAP
Benign
0.079
D
MetaRNN
Benign
0.37
T;T;T
MetaSVM
Benign
-0.40
T
MutationAssessor
Uncertain
2.5
M;M;M
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-3.8
.;D;D
REVEL
Uncertain
0.38
Sift
Uncertain
0.0010
.;D;D
Sift4G
Uncertain
0.011
.;D;D
Polyphen
0.99
.;.;D
Vest4
0.73, 0.54
MutPred
0.50
Gain of MoRF binding (P = 0.0165);Gain of MoRF binding (P = 0.0165);Gain of MoRF binding (P = 0.0165);
MVP
0.74
MPC
1.0
ClinPred
0.99
D
GERP RS
-7.3
Varity_R
0.70
gMVP
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-31273095; API