chrX-12718087-C-T

Variant names:

• chrX-12718087-C-T
• rs776961749
• NM_001368397.1:c.3261C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP7 BS2

The NM_001368397.1(FRMPD4):​c.3261C>T​(p.Arg1087Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 1,208,591 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.000022 (0 hom. 10 hem.)
• Consequence: FRMPD4 NM_001368397.1 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.113
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=0.113 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 10 XL gene

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.3261C>T	p.Arg1087Arg	synonymous	Exon 16 of 17	NP_001355326.1	A0A6Q8PH73
	FRMPD4	NM_001368395.3		c.3372C>T	p.Arg1124Arg	synonymous	Exon 18 of 19	NP_001355324.1
	FRMPD4	NM_001368396.3		c.3267C>T	p.Arg1089Arg	synonymous	Exon 16 of 17	NP_001355325.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD4	ENST00000675598.1	MANE Select	c.3261C>T	p.Arg1087Arg	synonymous	Exon 16 of 17	ENSP00000502607.1	A0A6Q8PH73
	FRMPD4	ENST00000380682.5	TSL:1	c.3261C>T	p.Arg1087Arg	synonymous	Exon 16 of 17	ENSP00000370057.1	Q14CM0
	FRMPD4	ENST00000656302.1		c.3315C>T	p.Arg1105Arg	synonymous	Exon 18 of 19	ENSP00000499481.1	A0A590UJL7

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111872 Hom.: 0 Cov.: 24

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: 0.000752

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000491 AC: 9 AN: 183342 AF XY: 0.0000590

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000219 AC: 24 AN: 1096663 Hom.: 0 Cov.: 32 AF XY: 0.0000276 AC XY: 10 AN XY: 362049

African (AFR) AF: 0.00 AC: 0 AN: 26368

American (AMR) AF: 0.00 AC: 0 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

East Asian (EAS) AF: 0.00 AC: 0 AN: 30200

South Asian (SAS) AF: 0.000425 AC: 23 AN: 54115

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 840681

Other (OTH) AF: 0.00 AC: 0 AN: 46048

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111928 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34132

African (AFR) AF: 0.00 AC: 0 AN: 30782

American (AMR) AF: 0.00 AC: 0 AN: 10686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3544

South Asian (SAS) AF: 0.000754 AC: 2 AN: 2652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6071

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53113

Other (OTH) AF: 0.00 AC: 0 AN: 1525

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	-0.46
CADD	Benign	6.6
DANN	Benign	0.57
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism

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: rs776961749; hg19: chrX-12736206;