11-64212171-G-T

Position:

• chr11-64212171-G-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FERMT3	NM_031471.6	c.786+424G>T		intron_variant		ENST00000345728.10	NP_113659.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FERMT3	ENST00000345728.10	c.786+424G>T		intron_variant		1	NM_031471.6	ENSP00000339950	P4

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

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.214

Alfa AF: 0.194 Hom.: 3761

Bravo AF: 0.183

Asia WGS AF: 0.240 AC: 833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.88
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs12575642; hg19: chr11-63979643;