rs5930546

Variant names:

• chrX-132100705-G-A
• rs5930546
• NM_194277.3:c.69C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_194277.3(FRMD7):​c.69C>T​(p.Ser23Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0984 in 1,194,992 control chromosomes in the GnomAD database, including 4,326 homozygotes. There are 37,694 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.084 (361 hom., 2700 hem., cov: 23)
  • Exomes 𝑓: 0.10 (3965 hom. 34994 hem.)
• Consequence: FRMD7 NM_194277.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.727

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant X-132100705-G-A is Benign according to our data. Variant chrX-132100705-G-A is described in ClinVar as [Benign]. Clinvar id is 263089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-132100705-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.727 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD7	NM_194277.3	c.69C>T	p.Ser23Ser	synonymous_variant	Exon 2 of 12	ENST00000298542.9	NP_919253.1
FRMD7	NM_001306193.2	c.69C>T	p.Ser23Ser	synonymous_variant	Exon 2 of 12		NP_001293122.1
FRMD7	XM_017029947.3	c.21C>T	p.Ser7Ser	synonymous_variant	Exon 2 of 12		XP_016885436.1
FRMD7	XM_017029948.3	c.30-6566C>T		intron_variant	Intron 1 of 8		XP_016885437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD7	ENST00000298542.9	c.69C>T	p.Ser23Ser	synonymous_variant	Exon 2 of 12	1	NM_194277.3	ENSP00000298542.3
FRMD7	ENST00000464296.1	c.69C>T	p.Ser23Ser	synonymous_variant	Exon 2 of 12	1		ENSP00000417996.1
FRMD7	ENST00000687717.1	n.327C>T		non_coding_transcript_exon_variant	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.0836 AC: 9334 AN: 111596 Hom.: 361 Cov.: 23 AF XY: 0.0796 AC XY: 2691 AN XY: 33800

Gnomad AFR AF: 0.0587

Gnomad AMI AF: 0.0613

Gnomad AMR AF: 0.0465

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.00168

Gnomad SAS AF: 0.0832

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0894

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0868

GnomAD3 exomes AF: 0.0840 AC: 15323 AN: 182485 Hom.: 462 AF XY: 0.0869 AC XY: 5827 AN XY: 67081

Gnomad AFR exome AF: 0.0580

Gnomad AMR exome AF: 0.0384

Gnomad ASJ exome AF: 0.0981

Gnomad EAS exome AF: 0.000650

Gnomad SAS exome AF: 0.0910

Gnomad FIN exome AF: 0.122

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.0939

GnomAD4 exome AF: 0.100 AC: 108292 AN: 1083347 Hom.: 3965 Cov.: 28 AF XY: 0.0998 AC XY: 34994 AN XY: 350707

Gnomad4 AFR exome AF: 0.0570

Gnomad4 AMR exome AF: 0.0397

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.000332

Gnomad4 SAS exome AF: 0.0924

Gnomad4 FIN exome AF: 0.117

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.0876

GnomAD4 genome AF: 0.0836 AC: 9337 AN: 111645 Hom.: 361 Cov.: 23 AF XY: 0.0797 AC XY: 2700 AN XY: 33859

Gnomad4 AFR AF: 0.0588

Gnomad4 AMR AF: 0.0464

Gnomad4 ASJ AF: 0.0873

Gnomad4 EAS AF: 0.00169

Gnomad4 SAS AF: 0.0835

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0858

Alfa AF: 0.0997 Hom.: 4004

Bravo AF: 0.0772

EpiCase AF: 0.109

EpiControl AF: 0.102

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nystagmus 1, congenital, X-linked Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.055
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs5930546; hg19: chrX-131234733;