rs137852209

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP5

The ENST00000464296.1(FRMD7):c.207G>A(p.Met69Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000923 in 1,083,026 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )

Consequence

FRMD7
ENST00000464296.1 missense, splice_region

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.28

Publications

5 publications found

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]

FRMD7 Gene-Disease associations (from GenCC):

nystagmus 1, congenital, X-linked
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

FRMD7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant X-132097298-C-T is Pathogenic according to our data. Variant chrX-132097298-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 10785.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD7	NM_194277.3 link	c.252G>A	p.Val84Val	synonymous_variant	Exon 4 of 12	ENST00000298542.9	NP_919253.1	Q6ZUT3-1
FRMD7	NM_001306193.2 link	c.207G>A	p.Met69Ile	missense_variant, splice_region_variant	Exon 4 of 12		NP_001293122.1	Q6ZUT3-2
FRMD7	XM_017029947.3 link	c.204G>A	p.Val68Val	synonymous_variant	Exon 4 of 12		XP_016885436.1
FRMD7	XM_017029948.3 link	c.30-3159G>A		intron_variant	Intron 1 of 8		XP_016885437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD7	ENST00000464296.1 link	c.207G>A	p.Met69Ile	missense_variant, splice_region_variant	Exon 4 of 12	1		ENSP00000417996.1		Q6ZUT3-2
FRMD7	ENST00000298542.9 link	c.252G>A	p.Val84Val	synonymous_variant	Exon 4 of 12	1	NM_194277.3	ENSP00000298542.3		Q6ZUT3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.23e-7

AC:

AN:

1083026

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

350210

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26110

American (AMR)

AF:

0.00

AC:

AN:

35194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19287

East Asian (EAS)

AF:

0.00

AC:

AN:

30155

South Asian (SAS)

AF:

0.00

AC:

AN:

53792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4105

European-Non Finnish (NFE)

AF:

0.00000121

AC:

AN:

828251

Other (OTH)

AF:

0.00

AC:

AN:

45600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Nystagmus 1, congenital, X-linked

Pathogenic:1

Nov 01, 2006

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

(source)

DANN

Benign

0.96

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.36

M_CAP

Benign

0.068

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.84

PhyloP100

3.3

PROVEAN

Benign

-0.33

REVEL

Benign

0.14

Sift

Benign

0.32

Sift4G

Benign

0.39

Polyphen

0.0

Vest4

0.45

MutPred

0.45

Gain of catalytic residue at P71 (P = 0.0282);

MVP

0.82

ClinPred

0.52

GERP RS

5.3

Mutation Taster

=27/73

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.41

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.41

Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over