rs11603538

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-64219241-C-A
• chr11-64219241-C-G
• chr11-64219241-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_031471.6(FERMT3):​c.787-10C>A variant causes a 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 intron
• Scores: Splicing: ADA: 0.00009313
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.52
• Publications: 11 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: Benign. The variant received -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 VariationId is 402862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

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>A		intron	N/A	NP_113659.3
	FERMT3	NM_001382362.1		c.787-10C>A		intron	N/A	NP_001369291.1
	FERMT3	NM_178443.3		c.787-10C>A		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>A		intron	N/A	ENSP00000339950.5
	FERMT3	ENST00000279227.10	TSL:1	c.787-10C>A		intron	N/A	ENSP00000279227.5
	FERMT3	ENST00000698865.1		c.798C>A	p.Pro266Pro	synonymous	Exon 7 of 15	ENSP00000513992.1

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

GnomAD2 exomes AF: 0.328 AC: 61757 AN: 188526 AF XY: 0.324

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 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

African (AFR) AF: 0.307 AC: 9900 AN: 32244

American (AMR) AF: 0.410 AC: 15837 AN: 38650

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 6628 AN: 25464

East Asian (EAS) AF: 0.315 AC: 11637 AN: 36914

South Asian (SAS) AF: 0.273 AC: 22158 AN: 81306

European-Finnish (FIN) AF: 0.304 AC: 15267 AN: 50144

Middle Eastern (MID) AF: 0.266 AC: 1520 AN: 5720

European-Non Finnish (NFE) AF: 0.358 AC: 390962 AN: 1092390

Other (OTH) AF: 0.342 AC: 20170 AN: 58908

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

African (AFR) AF: 0.307 AC: 12731 AN: 41506

American (AMR) AF: 0.398 AC: 6090 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 910 AN: 3470

East Asian (EAS) AF: 0.291 AC: 1501 AN: 5152

South Asian (SAS) AF: 0.278 AC: 1341 AN: 4826

European-Finnish (FIN) AF: 0.296 AC: 3126 AN: 10568

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.352 AC: 23939 AN: 67970

Other (OTH) AF: 0.339 AC: 714 AN: 2108

Alfa AF: 0.332 Hom.: 3338

Bravo AF: 0.340

Asia WGS AF: 0.336 AC: 1166 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.011
DANN	Benign	0.61
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11603538; hg19: chr11-63986713; COSMIC: COSV107232884; COSMIC: COSV107232884;