X-132077207-T-A

Position:

• chrX-132077207-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_194277.3(FRMD7):​c.*665A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 110,309 control chromosomes in the GnomAD database, including 4,593 homozygotes. There are 9,740 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (4593 hom., 9740 hem., cov: 22)
  • Exomes 𝑓: 0.19 (0 hom. 0 hem.)
• Consequence: FRMD7 NM_194277.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0410

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant X-132077207-T-A is Benign according to our data. Variant chrX-132077207-T-A is described in ClinVar as [Benign]. Clinvar id is 367900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD7	NM_194277.3	c.*665A>T		3_prime_UTR_variant	12/12	ENST00000298542.9	NP_919253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD7	ENST00000298542.9	c.*665A>T		3_prime_UTR_variant	12/12	1	NM_194277.3	ENSP00000298542.3
FRMD7	ENST00000370879.5	c.*665A>T		3_prime_UTR_variant	8/8	1		ENSP00000359916.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 35298 AN: 110230 Hom.: 4589 Cov.: 22 AF XY: 0.298 AC XY: 9706 AN XY: 32546

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.0981

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.352

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.312

GnomAD4 exome AF: 0.188 AC: 6 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.320 AC: 35324 AN: 110277 Hom.: 4593 Cov.: 22 AF XY: 0.299 AC XY: 9740 AN XY: 32603

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.0967

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.308

Alfa AF: 0.331 Hom.: 2101

Bravo AF: 0.318

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Nystagmus 1, congenital, X-linked Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.61
DANN	Benign	0.47

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

Other links and lift over

dbSNP: rs3764771; hg19: chrX-131211235;