chr11-64211394-C-G

Variant names:

• chr11-64211394-C-G
• rs369072342
• NM_031471.6:c.634C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031471.6(FERMT3):​c.634C>G​(p.Arg212Gly) 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. 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. R212H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FERMT3 NM_031471.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 1 publications found

Genes affected

FERMT3 (HGNC:23151): (FERM domain containing kindlin 3) Kindlins are a small family of proteins that mediate protein-protein interactions involved in integrin activation and thereby have a role in cell adhesion, migration, differentiation, and proliferation. The protein encoded by this gene has a key role in the regulation of hemostasis and thrombosis. This protein may also help maintain the membrane skeleton of erythrocytes. Mutations in this gene cause the autosomal recessive leukocyte adhesion deficiency syndrome-III (LAD-III). Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2010]

FERMT3 Gene-Disease associations (from GenCC):

• leukocyte adhesion deficiency 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17740166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FERMT3	NM_031471.6	c.634C>G	p.Arg212Gly	missense_variant	Exon 5 of 15	ENST00000345728.10	NP_113659.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FERMT3	ENST00000345728.10	c.634C>G	p.Arg212Gly	missense_variant	Exon 5 of 15	1	NM_031471.6	ENSP00000339950.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000433 AC: 1 AN: 231194 AF XY: 0.00

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: 0.00000963

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.062	T;D;.;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.74	T;T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.75	.;N;N;.
PhyloP100		1.5
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Benign	0.043
Sift	Benign	0.076	T;T;T;T
Sift4G	Uncertain	0.030	D;T;T;T
Polyphen		0.93, 0.065	.;P;B;.
Vest4		0.37, 0.39
MutPred		0.20		Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);.;
MVP		0.51
MPC		0.63
ClinPred		0.27	T
GERP RS		3.5
Varity_R		0.46
gMVP		0.31
Mutation Taster		=66/34	polymorphism

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: rs369072342; hg19: chr11-63978866;