chr20-6075045-G-GT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_017671.5(FERMT1):​c.*2127_*2128insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 133,236 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 4 hom., cov: 31)
Exomes 𝑓: 0.0079 ( 0 hom. )

Consequence

FERMT1
NM_017671.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.90
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 Likely_benign. Variant got -5 ACMG points.

BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00134 (178/133110) while in subpopulation EAS AF= 0.00771 (36/4668). AF 95% confidence interval is 0.00573. There are 4 homozygotes in gnomad4. There are 93 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FERMT1NM_017671.5 linkuse as main transcriptc.*2127_*2128insA 3_prime_UTR_variant 15/15 ENST00000217289.9 NP_060141.3
FERMT1XM_024451935.2 linkuse as main transcriptc.*2127_*2128insA 3_prime_UTR_variant 15/15 XP_024307703.1
FERMT1XM_047440259.1 linkuse as main transcriptc.*2127_*2128insA 3_prime_UTR_variant 15/15 XP_047296215.1
FERMT1XM_047440260.1 linkuse as main transcriptc.*2127_*2128insA 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.*2127_*2128insA 3_prime_UTR_variant 15/151 NM_017671.5 ENSP00000217289 P1Q9BQL6-1
FERMT1ENST00000478194.1 linkuse as main transcriptn.3121_3122insA non_coding_transcript_exon_variant 7/71

Frequencies

GnomAD3 genomes
AF:
0.00134
AC:
178
AN:
133072
Hom.:
4
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000696
Gnomad AMI
AF:
0.00694
Gnomad AMR
AF:
0.00199
Gnomad ASJ
AF:
0.000917
Gnomad EAS
AF:
0.00790
Gnomad SAS
AF:
0.00192
Gnomad FIN
AF:
0.000551
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00107
Gnomad OTH
AF:
0.00162
GnomAD4 exome
AF:
0.00794
AC:
1
AN:
126
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
68
show subpopulations
Gnomad4 EAS exome
AF:
0.00794
GnomAD4 genome
AF:
0.00134
AC:
178
AN:
133110
Hom.:
4
Cov.:
31
AF XY:
0.00145
AC XY:
93
AN XY:
64272
show subpopulations
Gnomad4 AFR
AF:
0.000694
Gnomad4 AMR
AF:
0.00199
Gnomad4 ASJ
AF:
0.000917
Gnomad4 EAS
AF:
0.00771
Gnomad4 SAS
AF:
0.00192
Gnomad4 FIN
AF:
0.000551
Gnomad4 NFE
AF:
0.00107
Gnomad4 OTH
AF:
0.00215
Alfa
AF:
0.000491
Hom.:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Kindler syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

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: rs139990090; hg19: chr20-6055692; API