11-64211102-GAGAAGA-G

Variant names:

• chr11-64211102-GAGAAGA-G
• rs759155629
• NM_031471.6:c.453_458delGAAGAA

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP3

The NM_031471.6(FERMT3):​c.453_458delGAAGAA​(p.Lys152_Lys153del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FERMT3 NM_031471.6 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.44
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_031471.6

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031471.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FERMT3	NM_031471.6	MANE Select	c.453_458delGAAGAA	p.Lys152_Lys153del	disruptive_inframe_deletion	Exon 4 of 15	NP_113659.3
	FERMT3	NM_001382362.1		c.453_458delGAAGAA	p.Lys152_Lys153del	disruptive_inframe_deletion	Exon 4 of 15	NP_001369291.1
	FERMT3	NM_178443.3		c.453_458delGAAGAA	p.Lys152_Lys153del	disruptive_inframe_deletion	Exon 4 of 15	NP_848537.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FERMT3	ENST00000345728.10	TSL:1 MANE Select	c.453_458delGAAGAA	p.Lys152_Lys153del	disruptive_inframe_deletion	Exon 4 of 15	ENSP00000339950.5
	FERMT3	ENST00000279227.10	TSL:1	c.453_458delGAAGAA	p.Lys152_Lys153del	disruptive_inframe_deletion	Exon 4 of 15	ENSP00000279227.5
	FERMT3	ENST00000698865.1		c.453_458delGAAGAA	p.Lys152_Lys153del	disruptive_inframe_deletion	Exon 4 of 15	ENSP00000513992.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.4
Mutation Taster		=115/85	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs759155629; hg19: chr11-63978574;