20-6075049-G-GT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_017671.5(FERMT1):​c.*2123_*2124insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 129,034 control chromosomes in the GnomAD database, including 1,956 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.17 ( 1956 hom., cov: 22)
Exomes 𝑓: 0.14 ( 0 hom. )

Consequence

FERMT1
NM_017671.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.184
Variant links:
Genes affected
FERMT1 (HGNC:15889): (FERM domain containing kindlin 1) This gene encodes a member of the fermitin family, and contains a FERM domain and a pleckstrin homology domain. The encoded protein is involved in integrin signaling and linkage of the actin cytoskeleton to the extracellular matrix. Mutations in this gene have been linked to Kindler syndrome. [provided by RefSeq, Dec 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FERMT1NM_017671.5 linkuse as main transcriptc.*2123_*2124insA 3_prime_UTR_variant 15/15 ENST00000217289.9 NP_060141.3
FERMT1XM_024451935.2 linkuse as main transcriptc.*2123_*2124insA 3_prime_UTR_variant 15/15 XP_024307703.1
FERMT1XM_047440259.1 linkuse as main transcriptc.*2123_*2124insA 3_prime_UTR_variant 15/15 XP_047296215.1
FERMT1XM_047440260.1 linkuse as main transcriptc.*2123_*2124insA 3_prime_UTR_variant 14/14 XP_047296216.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FERMT1ENST00000217289.9 linkuse as main transcriptc.*2123_*2124insA 3_prime_UTR_variant 15/151 NM_017671.5 ENSP00000217289 P1Q9BQL6-1
FERMT1ENST00000478194.1 linkuse as main transcriptn.3117_3118insA non_coding_transcript_exon_variant 7/71

Frequencies

GnomAD3 genomes
AF:
0.167
AC:
21527
AN:
128952
Hom.:
1954
Cov.:
22
show subpopulations
Gnomad AFR
AF:
0.101
Gnomad AMI
AF:
0.160
Gnomad AMR
AF:
0.194
Gnomad ASJ
AF:
0.125
Gnomad EAS
AF:
0.00935
Gnomad SAS
AF:
0.129
Gnomad FIN
AF:
0.292
Gnomad MID
AF:
0.116
Gnomad NFE
AF:
0.197
Gnomad OTH
AF:
0.138
GnomAD4 exome
AF:
0.136
AC:
9
AN:
66
Hom.:
0
Cov.:
0
AF XY:
0.194
AC XY:
7
AN XY:
36
show subpopulations
Gnomad4 EAS exome
AF:
0.136
GnomAD4 genome
AF:
0.167
AC:
21532
AN:
128968
Hom.:
1956
Cov.:
22
AF XY:
0.168
AC XY:
10440
AN XY:
62024
show subpopulations
Gnomad4 AFR
AF:
0.101
Gnomad4 AMR
AF:
0.195
Gnomad4 ASJ
AF:
0.125
Gnomad4 EAS
AF:
0.00938
Gnomad4 SAS
AF:
0.129
Gnomad4 FIN
AF:
0.292
Gnomad4 NFE
AF:
0.197
Gnomad4 OTH
AF:
0.136

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Kindler syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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.

Other links and lift over

dbSNP: rs11405989; hg19: chr20-6055696; API