11-64220444-G-A

Variant names:

• chr11-64220444-G-A
• rs76744324
• NM_031471.6:c.1320G>A

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.1320G>A​(p.Gln440Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,611,164 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (45 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (44 hom.)
• Consequence: FERMT3 NM_031471.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.55
• Publications: 1 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 (MetaRNN=0.005191624).
• BP6: Variant 11-64220444-G-A is Benign according to our data. Variant chr11-64220444-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 470171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.55 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0128 (1943/152340) while in subpopulation AFR AF = 0.0445 (1850/41564). AF 95% confidence interval is 0.0428. There are 45 homozygotes in GnomAd4. There are 935 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 45 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FERMT3	NM_031471.6	MANE Select	c.1320G>A	p.Gln440Gln	synonymous	Exon 12 of 15	NP_113659.3
	FERMT3	NM_001382362.1		c.1332G>A	p.Gln444Gln	synonymous	Exon 12 of 15	NP_001369291.1
	FERMT3	NM_178443.3		c.1332G>A	p.Gln444Gln	synonymous	Exon 12 of 15	NP_848537.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FERMT3	ENST00000345728.10	TSL:1 MANE Select	c.1320G>A	p.Gln440Gln	synonymous	Exon 12 of 15	ENSP00000339950.5
	FERMT3	ENST00000279227.10	TSL:1	c.1332G>A	p.Gln444Gln	synonymous	Exon 12 of 15	ENSP00000279227.5
	FERMT3	ENST00000698865.1		c.1341G>A	p.Gln447Gln	synonymous	Exon 12 of 15	ENSP00000513992.1

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1943 AN: 152222 Hom.: 45 Cov.: 33

Gnomad AFR AF: 0.0446

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00425

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00296 AC: 717 AN: 242546 AF XY: 0.00208

Gnomad AFR exome AF: 0.0441

Gnomad AMR exome AF: 0.00126

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000275

Gnomad OTH exome AF: 0.000672

GnomAD4 exome AF: 0.00125 AC: 1821 AN: 1458824 Hom.: 44 Cov.: 33 AF XY: 0.00105 AC XY: 761 AN XY: 725814

African (AFR) AF: 0.0471 AC: 1574 AN: 33444

American (AMR) AF: 0.00173 AC: 77 AN: 44482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51364

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5764

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1111446

Other (OTH) AF: 0.00224 AC: 135 AN: 60314

GnomAD4 genome AF: 0.0128 AC: 1943 AN: 152340 Hom.: 45 Cov.: 33 AF XY: 0.0126 AC XY: 935 AN XY: 74484

African (AFR) AF: 0.0445 AC: 1850 AN: 41564

American (AMR) AF: 0.00425 AC: 65 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68024

Other (OTH) AF: 0.0109 AC: 23 AN: 2116

Alfa AF: 0.00372 Hom.: 3

Bravo AF: 0.0137

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0398 AC: 175

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.00367 AC: 444

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leukocyte adhesion deficiency 3 Benign:2

Mar 17, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	5.3
DANN	Benign	0.97
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-0.99	T
PhyloP100		2.6
PROVEAN	Benign	0.31	N
REVEL	Benign	0.013
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
MVP		0.55
ClinPred		0.039	T
GERP RS		1.4
PromoterAI		0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs76744324; hg19: chr11-63987916;