rs5975315

Variant names:

• chrX-132077438-G-A
• rs5975315
• NM_194277.3:c.*434C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_194277.3(FRMD7):​c.*434C>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 0.0172 in 139,696 control chromosomes in the GnomAD database, including 68 homozygotes. There are 639 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (66 hom., 624 hem., cov: 23)
  • Exomes 𝑓: 0.0021 (2 hom. 15 hem.)
• Consequence: FRMD7 NM_194277.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0510
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant X-132077438-G-A is Benign according to our data. Variant chrX-132077438-G-A is described in ClinVar as Benign. ClinVar VariationId is 367903.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0699 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.*434C>T		3_prime_UTR	Exon 12 of 12	NP_919253.1	Q6ZUT3-1
	FRMD7	NM_001306193.2		c.*434C>T		3_prime_UTR	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.*434C>T		3_prime_UTR	Exon 12 of 12	ENSP00000298542.3	Q6ZUT3-1
	FRMD7	ENST00000370879.5	TSL:1	c.*434C>T		3_prime_UTR	Exon 8 of 8	ENSP00000359916.1	X6R7S7

Frequencies

GnomAD3 genomes AF: 0.0209 AC: 2338 AN: 112003 Hom.: 66 Cov.: 23

Gnomad AFR AF: 0.0725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00671

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000738

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00422

Gnomad NFE AF: 0.000282

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.00213 AC: 59 AN: 27638 Hom.: 2 Cov.: 0 AF XY: 0.00280 AC XY: 15 AN XY: 5366

African (AFR) AF: 0.0655 AC: 43 AN: 656

American (AMR) AF: 0.00379 AC: 9 AN: 2372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 693

East Asian (EAS) AF: 0.00 AC: 0 AN: 1710

South Asian (SAS) AF: 0.000515 AC: 1 AN: 1942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1216

Middle Eastern (MID) AF: 0.0108 AC: 1 AN: 93

European-Non Finnish (NFE) AF: 0.000115 AC: 2 AN: 17362

Other (OTH) AF: 0.00188 AC: 3 AN: 1594

GnomAD4 genome AF: 0.0209 AC: 2339 AN: 112058 Hom.: 66 Cov.: 23 AF XY: 0.0182 AC XY: 624 AN XY: 34252

African (AFR) AF: 0.0724 AC: 2232 AN: 30833

American (AMR) AF: 0.00670 AC: 71 AN: 10597

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3583

South Asian (SAS) AF: 0.000740 AC: 2 AN: 2702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6092

Middle Eastern (MID) AF: 0.00461 AC: 1 AN: 217

European-Non Finnish (NFE) AF: 0.000282 AC: 15 AN: 53183

Other (OTH) AF: 0.0118 AC: 18 AN: 1523

Alfa AF: 0.0177 Hom.: 51

Bravo AF: 0.0247

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Nystagmus 1, congenital, X-linked (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		0.051
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: rs5975315; hg19: chrX-131211466;