chrX-132078916-A-G

Variant names:

• chrX-132078916-A-G
• rs7051368
• NM_194277.3:c.1101T>C

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.1101T>C​(p.Asn367Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0889 in 1,205,850 control chromosomes in the GnomAD database, including 3,561 homozygotes. There are 33,772 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.086 (318 hom., 2541 hem., cov: 22)
  • Exomes 𝑓: 0.089 (3243 hom. 31231 hem.)
• Consequence: FRMD7 NM_194277.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.160
• Publications: 2 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=-0.6).
• BP6: Variant X-132078916-A-G is Benign according to our data. Variant chrX-132078916-A-G is described in ClinVar as Benign. ClinVar VariationId is 263086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0959 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.1101T>C	p.Asn367Asn	synonymous	Exon 12 of 12	NP_919253.1	Q6ZUT3-1
	FRMD7	NM_001306193.2		c.1056T>C	p.Asn352Asn	synonymous	Exon 12 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.1101T>C	p.Asn367Asn	synonymous	Exon 12 of 12	ENSP00000298542.3	Q6ZUT3-1
	FRMD7	ENST00000464296.1	TSL:1	c.1056T>C	p.Asn352Asn	synonymous	Exon 12 of 12	ENSP00000417996.1	Q6ZUT3-2
	FRMD7	ENST00000370879.5	TSL:1	c.741T>C	p.Asn247Asn	synonymous	Exon 8 of 8	ENSP00000359916.1	X6R7S7

Frequencies

GnomAD3 genomes AF: 0.0856 AC: 9517 AN: 111142 Hom.: 317 Cov.: 22

Gnomad AFR AF: 0.0916

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0599

Gnomad ASJ AF: 0.0523

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0150

Gnomad FIN AF: 0.0906

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.0982

Gnomad OTH AF: 0.0927

GnomAD2 exomes AF: 0.0688 AC: 12461 AN: 181051 AF XY: 0.0666

Gnomad AFR exome AF: 0.0938

Gnomad AMR exome AF: 0.0372

Gnomad ASJ exome AF: 0.0494

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0836

Gnomad NFE exome AF: 0.0985

Gnomad OTH exome AF: 0.0781

GnomAD4 exome AF: 0.0892 AC: 97648 AN: 1094652 Hom.: 3243 Cov.: 30 AF XY: 0.0867 AC XY: 31231 AN XY: 360286

African (AFR) AF: 0.0980 AC: 2581 AN: 26339

American (AMR) AF: 0.0399 AC: 1404 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 1005 AN: 19367

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30188

South Asian (SAS) AF: 0.0163 AC: 882 AN: 54060

European-Finnish (FIN) AF: 0.0841 AC: 3405 AN: 40493

Middle Eastern (MID) AF: 0.111 AC: 457 AN: 4119

European-Non Finnish (NFE) AF: 0.100 AC: 84073 AN: 838902

Other (OTH) AF: 0.0835 AC: 3840 AN: 45980

GnomAD4 genome AF: 0.0857 AC: 9527 AN: 111198 Hom.: 318 Cov.: 22 AF XY: 0.0760 AC XY: 2541 AN XY: 33432

African (AFR) AF: 0.0918 AC: 2809 AN: 30597

American (AMR) AF: 0.0598 AC: 625 AN: 10448

Ashkenazi Jewish (ASJ) AF: 0.0523 AC: 138 AN: 2641

East Asian (EAS) AF: 0.00 AC: 0 AN: 3514

South Asian (SAS) AF: 0.0143 AC: 38 AN: 2657

European-Finnish (FIN) AF: 0.0906 AC: 537 AN: 5929

Middle Eastern (MID) AF: 0.107 AC: 23 AN: 214

European-Non Finnish (NFE) AF: 0.0982 AC: 5203 AN: 52999

Other (OTH) AF: 0.0916 AC: 139 AN: 1518

Alfa AF: 0.0912 Hom.: 4553

Bravo AF: 0.0845

EpiCase AF: 0.0990

EpiControl AF: 0.0990

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	-0.60
CADD	Benign	0.68
DANN	Benign	0.63
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7051368; hg19: chrX-131212944; COSMIC: COSV53745461; COSMIC: COSV53745461;