rs797045589

Variant names:

• chrX-12716613-C-T
• rs797045589
• NM_001368397.1:c.2154C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001368397.1(FRMPD4):​c.2154C>T​(p.Asn718Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000895 in 111,774 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 22)
• Consequence: FRMPD4 NM_001368397.1 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28
• Publications: 0 publications found

Genes affected

FRMPD4 (HGNC:29007): (FERM and PDZ domain containing 4) This gene encodes a multi-domain (WW, PDZ, FERM) containing protein. Through its interaction with other proteins (such as PSD-95), it functions as a positive regulator of dendritic spine morphogenesis and density, and is required for the maintenance of excitatory synaptic transmission. [provided by RefSeq, Jan 2010]

FRMPD4 Gene-Disease associations (from GenCC):

• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, X-linked 104

  Inheritance: XL Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=1.28 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001368397.1. 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
	FRMPD4	NM_001368397.1	MANE Select	c.2154C>T	p.Asn718Asn	synonymous	Exon 15 of 17	NP_001355326.1	A0A6Q8PH73
	FRMPD4	NM_001368395.3		c.2265C>T	p.Asn755Asn	synonymous	Exon 17 of 19	NP_001355324.1
	FRMPD4	NM_001368396.3		c.2160C>T	p.Asn720Asn	synonymous	Exon 15 of 17	NP_001355325.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD4	ENST00000675598.1	MANE Select	c.2154C>T	p.Asn718Asn	synonymous	Exon 15 of 17	ENSP00000502607.1	A0A6Q8PH73
	FRMPD4	ENST00000380682.5	TSL:1	c.2154C>T	p.Asn718Asn	synonymous	Exon 15 of 17	ENSP00000370057.1	Q14CM0
	FRMPD4	ENST00000656302.1		c.2208C>T	p.Asn736Asn	synonymous	Exon 17 of 19	ENSP00000499481.1	A0A590UJL7

Frequencies

GnomAD3 genomes AF: 0.00000895 AC: 1 AN: 111774 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000663

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000895 AC: 1 AN: 111774 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33944

African (AFR) AF: 0.00 AC: 0 AN: 30748

American (AMR) AF: 0.00 AC: 0 AN: 10557

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3558

South Asian (SAS) AF: 0.00 AC: 0 AN: 2658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6049

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53120

Other (OTH) AF: 0.000663 AC: 1 AN: 1509

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.4
DANN	Benign	0.69
PhyloP100		1.3

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: rs797045589; hg19: chrX-12734732;