X-132077207-T-A

Variant names:

• chrX-132077207-T-A
• rs3764771
• NM_194277.3:c.*665A>T

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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 VariationId 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.

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.*665A>T		3_prime_UTR	Exon 12 of 12	NP_919253.1	Q6ZUT3-1
	FRMD7	NM_001306193.2		c.*665A>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.*665A>T		3_prime_UTR	Exon 12 of 12	ENSP00000298542.3	Q6ZUT3-1
	FRMD7	ENST00000370879.5	TSL:1	c.*665A>T		3_prime_UTR	Exon 8 of 8	ENSP00000359916.1	X6R7S7

Frequencies

GnomAD3 genomes AF: 0.320 AC: 35298 AN: 110230 Hom.: 4589 Cov.: 22

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.192 AC: 5 AN: 26

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.443 AC: 13391 AN: 30209

American (AMR) AF: 0.172 AC: 1788 AN: 10380

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 795 AN: 2627

East Asian (EAS) AF: 0.0967 AC: 340 AN: 3516

South Asian (SAS) AF: 0.196 AC: 518 AN: 2640

European-Finnish (FIN) AF: 0.288 AC: 1670 AN: 5803

Middle Eastern (MID) AF: 0.349 AC: 74 AN: 212

European-Non Finnish (NFE) AF: 0.307 AC: 16191 AN: 52701

Other (OTH) AF: 0.308 AC: 465 AN: 1510

Alfa AF: 0.331 Hom.: 2101

Bravo AF: 0.318

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.61
DANN	Benign	0.47
PhyloP100		0.041
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: rs3764771; hg19: chrX-131211235;