rs78810429

Variant names:

• chr11-64211062-C-T
• rs78810429
• NM_031471.6:c.405C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_031471.6(FERMT3):​c.405C>T​(p.His135His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,596,214 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0092 (10 hom., cov: 32)
  • Exomes 𝑓: 0.012 (125 hom.)
• Consequence: FERMT3 NM_031471.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.390
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 11-64211062-C-T is Benign according to our data. Variant chr11-64211062-C-T is described in ClinVar as Benign. ClinVar VariationId is 197359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.39 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00921 (1402/152280) while in subpopulation NFE AF = 0.013 (884/68004). AF 95% confidence interval is 0.0123. There are 10 homozygotes in GnomAd4. There are 681 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

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.405C>T	p.His135His	synonymous	Exon 4 of 15	NP_113659.3
	FERMT3	NM_001382362.1		c.405C>T	p.His135His	synonymous	Exon 4 of 15	NP_001369291.1	Q86UX7-1
	FERMT3	NM_178443.3		c.405C>T	p.His135His	synonymous	Exon 4 of 15	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.405C>T	p.His135His	synonymous	Exon 4 of 15	ENSP00000339950.5	Q86UX7-2
	FERMT3	ENST00000279227.10	TSL:1	c.405C>T	p.His135His	synonymous	Exon 4 of 15	ENSP00000279227.5	Q86UX7-1
	FERMT3	ENST00000698865.1		c.405C>T	p.His135His	synonymous	Exon 4 of 15	ENSP00000513992.1	A0A8V8TP41

Frequencies

GnomAD3 genomes AF: 0.00920 AC: 1400 AN: 152162 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.0128

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00919 AC: 1948 AN: 211888 AF XY: 0.00886

Gnomad AFR exome AF: 0.00213

Gnomad AMR exome AF: 0.00838

Gnomad ASJ exome AF: 0.0149

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0126

Gnomad NFE exome AF: 0.0121

Gnomad OTH exome AF: 0.00978

GnomAD4 exome AF: 0.0119 AC: 17247 AN: 1443934 Hom.: 125 Cov.: 35 AF XY: 0.0117 AC XY: 8394 AN XY: 716798

African (AFR) AF: 0.00168 AC: 55 AN: 32822

American (AMR) AF: 0.00866 AC: 368 AN: 42512

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 349 AN: 25664

East Asian (EAS) AF: 0.0000261 AC: 1 AN: 38380

South Asian (SAS) AF: 0.00559 AC: 467 AN: 83538

European-Finnish (FIN) AF: 0.0136 AC: 710 AN: 52090

Middle Eastern (MID) AF: 0.00418 AC: 24 AN: 5740

European-Non Finnish (NFE) AF: 0.0133 AC: 14668 AN: 1103532

Other (OTH) AF: 0.0101 AC: 605 AN: 59656

GnomAD4 genome AF: 0.00921 AC: 1402 AN: 152280 Hom.: 10 Cov.: 32 AF XY: 0.00915 AC XY: 681 AN XY: 74444

African (AFR) AF: 0.00233 AC: 97 AN: 41572

American (AMR) AF: 0.0114 AC: 174 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.00602 AC: 29 AN: 4820

European-Finnish (FIN) AF: 0.0128 AC: 136 AN: 10622

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0130 AC: 884 AN: 68004

Other (OTH) AF: 0.0118 AC: 25 AN: 2110

Alfa AF: 0.0108 Hom.: 6

Bravo AF: 0.00884

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Leukocyte adhesion deficiency 3 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.4
DANN	Benign	0.62
PhyloP100		0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs78810429; hg19: chr11-63978534;