NM_194277.3:c.69C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 263089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194277.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD7	NM_194277.3	MANE Select	c.69C>T	p.Ser23Ser	synonymous	Exon 2 of 12	NP_919253.1	Q6ZUT3-1
	FRMD7	NM_001306193.2		c.69C>T	p.Ser23Ser	synonymous	Exon 2 of 12	NP_001293122.1	Q6ZUT3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD7	ENST00000298542.9	TSL:1 MANE Select	c.69C>T	p.Ser23Ser	synonymous	Exon 2 of 12	ENSP00000298542.3	Q6ZUT3-1
	FRMD7	ENST00000464296.1	TSL:1	c.69C>T	p.Ser23Ser	synonymous	Exon 2 of 12	ENSP00000417996.1	Q6ZUT3-2
	FRMD7	ENST00000687717.1		n.327C>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.0836 AC: 9334 AN: 111596 Hom.: 361 Cov.: 23

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

GnomAD2 exomes AF: 0.0840 AC: 15323 AN: 182485 AF XY: 0.0869

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 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

African (AFR) AF: 0.0570 AC: 1490 AN: 26146

American (AMR) AF: 0.0397 AC: 1397 AN: 35193

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 1968 AN: 19287

East Asian (EAS) AF: 0.000332 AC: 10 AN: 30159

South Asian (SAS) AF: 0.0924 AC: 4971 AN: 53824

European-Finnish (FIN) AF: 0.117 AC: 4692 AN: 39999

Middle Eastern (MID) AF: 0.0943 AC: 387 AN: 4102

European-Non Finnish (NFE) AF: 0.108 AC: 89378 AN: 828973

Other (OTH) AF: 0.0876 AC: 3999 AN: 45664

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

African (AFR) AF: 0.0588 AC: 1808 AN: 30733

American (AMR) AF: 0.0464 AC: 491 AN: 10582

Ashkenazi Jewish (ASJ) AF: 0.0873 AC: 231 AN: 2645

East Asian (EAS) AF: 0.00169 AC: 6 AN: 3553

South Asian (SAS) AF: 0.0835 AC: 225 AN: 2696

European-Finnish (FIN) AF: 0.108 AC: 651 AN: 6024

Middle Eastern (MID) AF: 0.0849 AC: 18 AN: 212

European-Non Finnish (NFE) AF: 0.108 AC: 5735 AN: 52999

Other (OTH) AF: 0.0858 AC: 130 AN: 1516

Alfa AF: 0.0961 Hom.: 4882

Bravo AF: 0.0772

EpiCase AF: 0.109

EpiControl AF: 0.102

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Nystagmus 1, congenital, X-linked (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.055
DANN	Benign	0.66
PhyloP100		-0.73
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5930546; hg19: chrX-131234733;