chr11-64212171-G-T

Variant names:

• chr11-64212171-G-T
• rs12575642
• NM_031471.6:c.786+424G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031471.6(FERMT3):​c.786+424G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,198 control chromosomes in the GnomAD database, including 2,723 homozygotes. 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: 𝑓 0.18 (2723 hom., cov: 32)
• Consequence: FERMT3 NM_031471.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 24 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.284 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FERMT3	NM_031471.6	MANE Select	c.786+424G>T		intron	N/A	NP_113659.3
	FERMT3	NM_001382362.1		c.786+424G>T		intron	N/A	NP_001369291.1	Q86UX7-1
	FERMT3	NM_178443.3		c.786+424G>T		intron	N/A	NP_848537.1	Q86UX7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FERMT3	ENST00000345728.10	TSL:1 MANE Select	c.786+424G>T		intron	N/A	ENSP00000339950.5	Q86UX7-2
	FERMT3	ENST00000279227.10	TSL:1	c.786+424G>T		intron	N/A	ENSP00000279227.5	Q86UX7-1
	FERMT3	ENST00000698865.1		c.786+424G>T		intron	N/A	ENSP00000513992.1	A0A8V8TP41

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27157 AN: 152080 Hom.: 2720 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.179 AC: 27177 AN: 152198 Hom.: 2723 Cov.: 32 AF XY: 0.181 AC XY: 13482 AN XY: 74410

African (AFR) AF: 0.110 AC: 4578 AN: 41532

American (AMR) AF: 0.291 AC: 4452 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3470

East Asian (EAS) AF: 0.198 AC: 1025 AN: 5176

South Asian (SAS) AF: 0.200 AC: 967 AN: 4826

European-Finnish (FIN) AF: 0.182 AC: 1926 AN: 10598

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12944 AN: 67986

Other (OTH) AF: 0.214 AC: 452 AN: 2114

Alfa AF: 0.189 Hom.: 5904

Bravo AF: 0.183

Asia WGS AF: 0.240 AC: 833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.88
DANN	Benign	0.65
PhyloP100		-0.076
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs12575642; hg19: chr11-63979643;