chrX-132077947-ATCT-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_SupportingBS2

The NM_194277.3(FRMD7):​c.2067_2069delAGA​(p.Glu689del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000661 in 1,209,675 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 2 hem., cov: 23)
Exomes 𝑓: 0.0000046 ( 0 hom. 2 hem. )

Consequence

FRMD7
NM_194277.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.43
Variant links:
Genes affected
FRMD7 (HGNC:8079): (FERM domain containing 7) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of neuron projection development. Predicted to act upstream of or within several processes, including negative regulation of stress fiber assembly; positive regulation of lamellipodium assembly; and positive regulation of small GTPase mediated signal transduction. Located in cytosol; nucleoplasm; and plasma membrane. Implicated in congenital nystagmus 1. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM4
Nonframeshift variant in NON repetitive region in NM_194277.3. Strenght limited to Supporting due to length of the change: 1aa.
BS2
High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FRMD7NM_194277.3 linkc.2067_2069delAGA p.Glu689del disruptive_inframe_deletion Exon 12 of 12 ENST00000298542.9 NP_919253.1 Q6ZUT3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FRMD7ENST00000298542.9 linkc.2067_2069delAGA p.Glu689del disruptive_inframe_deletion Exon 12 of 12 1 NM_194277.3 ENSP00000298542.3 Q6ZUT3-1
FRMD7ENST00000464296.1 linkc.2022_2024delAGA p.Glu674del disruptive_inframe_deletion Exon 12 of 12 1 ENSP00000417996.1 Q6ZUT3-2
FRMD7ENST00000370879.5 linkc.1707_1709delAGA p.Glu569del disruptive_inframe_deletion Exon 8 of 8 1 ENSP00000359916.1 X6R7S7

Frequencies

GnomAD3 genomes
AF:
0.0000268
AC:
3
AN:
111954
Hom.:
0
Cov.:
23
AF XY:
0.0000587
AC XY:
2
AN XY:
34098
show subpopulations
Gnomad AFR
AF:
0.0000974
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000547
AC:
1
AN:
182785
Hom.:
0
AF XY:
0.0000148
AC XY:
1
AN XY:
67485
show subpopulations
Gnomad AFR exome
AF:
0.0000760
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000455
AC:
5
AN:
1097721
Hom.:
0
AF XY:
0.00000551
AC XY:
2
AN XY:
363159
show subpopulations
Gnomad4 AFR exome
AF:
0.0000379
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000356
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000268
AC:
3
AN:
111954
Hom.:
0
Cov.:
23
AF XY:
0.0000587
AC XY:
2
AN XY:
34098
show subpopulations
Gnomad4 AFR
AF:
0.0000974
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Jan 06, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant, c.2067_2069del, results in the deletion of 1 amino acid(s) of the FRMD7 protein (p.Glu689del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs745846839, gnomAD 0.008%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with FRMD7-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

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: rs745846839; hg19: chrX-131211975; API