Variant 11-64219559-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_031471.6(FERMT3):c.930G>T(p.Val310=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,611,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. V310V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

FERMT3
NM_031471.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.158

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 11-64219559-G-T is Benign according to our data. Variant chr11-64219559-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1084195.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.158 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0000919 (14/152284) while in subpopulation AFR AF= 0.000313 (13/41556). AF 95% confidence interval is 0.000185. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FERMT3	NM_031471.6 linkuse as main transcript	c.930G>T	p.Val310=	synonymous_variant	8/15	ENST00000345728.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FERMT3	ENST00000345728.10 linkuse as main transcript	c.930G>T	p.Val310=	synonymous_variant	8/15	1	NM_031471.6	P4	Q86UX7-2

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000244

AC:

AN:

245474

Hom.:

AF XY:

0.0000300

AC XY:

AN XY:

133370

show subpopulations

Gnomad AFR exome

AF:

0.000254

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000452

AC:

AN:

1459276

Hom.:

Cov.:

AF XY:

0.0000455

AC XY:

AN XY:

725846

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.0000919

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000831

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Leukocyte adhesion deficiency 3

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 28, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.6

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

3.2

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over