rs11603538

chr11-64219241-C-Achr11-64219241-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_031471.6(FERMT3):c.787-10C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,573,828 control chromosomes in the GnomAD database, including 95,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (8621 hom., cov: 33)
  • Exomes 𝑓: 0.35 (86786 hom.)
• Consequence: FERMT3 NM_031471.6 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00009313
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.52

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-64219241-C-A is Benign according to our data. Variant chr11-64219241-C-A is described in ClinVar as [Benign]. Clinvar id is 402862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64219241-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FERMT3	NM_031471.6	c.787-10C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000345728.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FERMT3	ENST00000345728.10	c.787-10C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_031471.6	P4

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50641 AN: 151968 Hom.: 8605 Cov.: 33

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.334

GnomAD3 exomes AF: 0.328 AC: 61757 AN: 188526 Hom.: 10308 AF XY: 0.324 AC XY: 32851 AN XY: 101388

Gnomad AFR exome AF: 0.303

Gnomad AMR exome AF: 0.404

Gnomad ASJ exome AF: 0.262

Gnomad EAS exome AF: 0.279

Gnomad SAS exome AF: 0.271

Gnomad FIN exome AF: 0.301

Gnomad NFE exome AF: 0.343

Gnomad OTH exome AF: 0.330

GnomAD4 exome AF: 0.348 AC: 494079 AN: 1421740 Hom.: 86786 Cov.: 36 AF XY: 0.345 AC XY: 242592 AN XY: 703964

Gnomad4 AFR exome AF: 0.307

Gnomad4 AMR exome AF: 0.410

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.315

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.358

Gnomad4 OTH exome AF: 0.342

GnomAD4 genome AF: 0.333 AC: 50694 AN: 152088 Hom.: 8621 Cov.: 33 AF XY: 0.331 AC XY: 24621 AN XY: 74334

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.339

Alfa AF: 0.332 Hom.: 3055

Bravo AF: 0.340

Asia WGS AF: 0.336 AC: 1166 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Leukocyte adhesion deficiency 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.011
Dann	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000093
dbscSNV1_RF	Benign	0.034
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11603538; hg19: chr11-63986713;