rs78038516

Variant names:

• chr11-64210595-C-G
• rs78038516
• NM_031471.6:c.161-16C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-64210595-C-G
• chr11-64210595-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_031471.6(FERMT3):​c.161-16C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,610,436 control chromosomes in the GnomAD database, including 18,988 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1165 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17823 hom.)
• Consequence: FERMT3 NM_031471.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0890
• Publications: 8 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: Orphanet, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-64210595-C-G is Benign according to our data. Variant chr11-64210595-C-G is described in ClinVar as Benign. ClinVar VariationId is 402861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 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.161-16C>G		intron	N/A	NP_113659.3
	FERMT3	NM_001382362.1		c.161-16C>G		intron	N/A	NP_001369291.1	Q86UX7-1
	FERMT3	NM_178443.3		c.161-16C>G		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.161-16C>G		intron	N/A	ENSP00000339950.5	Q86UX7-2
	FERMT3	ENST00000279227.10	TSL:1	c.161-16C>G		intron	N/A	ENSP00000279227.5	Q86UX7-1
	FERMT3	ENST00000698865.1		c.161-16C>G		intron	N/A	ENSP00000513992.1	A0A8V8TP41

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16843 AN: 152010 Hom.: 1165 Cov.: 32

Gnomad AFR AF: 0.0439

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.0961

Gnomad SAS AF: 0.0761

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.101

GnomAD2 exomes AF: 0.117 AC: 29230 AN: 249182 AF XY: 0.119

Gnomad AFR exome AF: 0.0426

Gnomad AMR exome AF: 0.0850

Gnomad ASJ exome AF: 0.0716

Gnomad EAS exome AF: 0.0875

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.151 AC: 220596 AN: 1458308 Hom.: 17823 Cov.: 34 AF XY: 0.149 AC XY: 107960 AN XY: 725168

African (AFR) AF: 0.0395 AC: 1319 AN: 33402

American (AMR) AF: 0.0858 AC: 3832 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 1849 AN: 26082

East Asian (EAS) AF: 0.128 AC: 5059 AN: 39642

South Asian (SAS) AF: 0.0750 AC: 6468 AN: 86204

European-Finnish (FIN) AF: 0.127 AC: 6784 AN: 53366

Middle Eastern (MID) AF: 0.0584 AC: 336 AN: 5754

European-Non Finnish (NFE) AF: 0.169 AC: 187089 AN: 1108988

Other (OTH) AF: 0.131 AC: 7860 AN: 60192

GnomAD4 genome AF: 0.111 AC: 16850 AN: 152128 Hom.: 1165 Cov.: 32 AF XY: 0.108 AC XY: 8021 AN XY: 74356

African (AFR) AF: 0.0440 AC: 1828 AN: 41514

American (AMR) AF: 0.0894 AC: 1366 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0761 AC: 264 AN: 3468

East Asian (EAS) AF: 0.0959 AC: 495 AN: 5162

South Asian (SAS) AF: 0.0766 AC: 370 AN: 4830

European-Finnish (FIN) AF: 0.114 AC: 1203 AN: 10596

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10959 AN: 67952

Other (OTH) AF: 0.0999 AC: 211 AN: 2112

Alfa AF: 0.0778 Hom.: 125

Bravo AF: 0.107

Asia WGS AF: 0.0850 AC: 294 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.35
PhyloP100		-0.089
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs78038516;

hg19: chr11-63978067;

COSMIC: COSV54181399;

COSMIC: COSV54181399;