11-64219241-C-G

Variant names:

• chr11-64219241-C-G
• rs11603538
• NM_031471.6:c.787-10C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031471.6(FERMT3):​c.787-10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,096 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: FERMT3 NM_031471.6 intron
• Scores: Splicing: ADA: 0.0003601
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.52
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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.787-10C>G		intron	N/A	NP_113659.3
	FERMT3	NM_001382362.1		c.787-10C>G		intron	N/A	NP_001369291.1
	FERMT3	NM_178443.3		c.787-10C>G		intron	N/A	NP_848537.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FERMT3	ENST00000345728.10	TSL:1 MANE Select	c.787-10C>G		intron	N/A	ENSP00000339950.5
	FERMT3	ENST00000279227.10	TSL:1	c.787-10C>G		intron	N/A	ENSP00000279227.5
	FERMT3	ENST00000698865.1		c.798C>G	p.Pro266Pro	synonymous	Exon 7 of 15	ENSP00000513992.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1422096 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 704150

African (AFR) AF: 0.00 AC: 0 AN: 32256

American (AMR) AF: 0.00 AC: 0 AN: 38662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25466

East Asian (EAS) AF: 0.00 AC: 0 AN: 36922

South Asian (SAS) AF: 0.00 AC: 0 AN: 81322

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1092650

Other (OTH) AF: 0.00 AC: 0 AN: 58924

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.010
DANN	Benign	0.22
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00036
dbscSNV1_RF	Benign	0.054
SpliceAI score (max)		0.14		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: rs11603538; hg19: chr11-63986713;