rs78038516

chr11-64210595-C-Gchr11-64210595-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.161-16C>G 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 0.147 in 1,610,436 control chromosomes in the GnomAD database, including 18,988 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1165 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17823 hom.)
• Consequence: FERMT3 NM_031471.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0890

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=-0.83).
• BP6: Variant 11-64210595-C-G is Benign according to our data. Variant chr11-64210595-C-G is described in ClinVar as [Benign]. Clinvar id is 402861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FERMT3	NM_031471.6	c.161-16C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000345728.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FERMT3	ENST00000345728.10	c.161-16C>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_031471.6	P4

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16843 AN: 152010 Hom.: 1165 Cov.: 32

Gnomad AFR AF: 0.0439

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.0961

Gnomad SAS AF: 0.0761

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.101

GnomAD3 exomes AF: 0.117 AC: 29230 AN: 249182 Hom.: 1982 AF XY: 0.119 AC XY: 16015 AN XY: 134894

Gnomad AFR exome AF: 0.0426

Gnomad AMR exome AF: 0.0850

Gnomad ASJ exome AF: 0.0716

Gnomad EAS exome AF: 0.0875

Gnomad SAS exome AF: 0.0724

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.151 AC: 220596 AN: 1458308 Hom.: 17823 Cov.: 34 AF XY: 0.149 AC XY: 107960 AN XY: 725168

Gnomad4 AFR exome AF: 0.0395

Gnomad4 AMR exome AF: 0.0858

Gnomad4 ASJ exome AF: 0.0709

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.0750

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.169

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.111 AC: 16850 AN: 152128 Hom.: 1165 Cov.: 32 AF XY: 0.108 AC XY: 8021 AN XY: 74356

Gnomad4 AFR AF: 0.0440

Gnomad4 AMR AF: 0.0894

Gnomad4 ASJ AF: 0.0761

Gnomad4 EAS AF: 0.0959

Gnomad4 SAS AF: 0.0766

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.0999

Alfa AF: 0.0778 Hom.: 125

Bravo AF: 0.107

Asia WGS AF: 0.0850 AC: 294 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	-0.83
Cadd	Benign	1.2
Dann	Benign	0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs78038516; hg19: chr11-63978067; COSMIC: COSV54181399; COSMIC: COSV54181399;