rs1555897781

Variant names:

• chrX-12716383-G-A
• rs1555897781
• NM_001368397.1:c.1924G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-12716383-G-A
• chrX-12716383-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001368397.1(FRMPD4):​c.1924G>A​(p.Ala642Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A642V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 22)
• Consequence: FRMPD4 NM_001368397.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66
• 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Illumina
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0777953).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD4	NM_001368397.1	MANE Select	c.1924G>A	p.Ala642Thr	missense	Exon 15 of 17	NP_001355326.1
	FRMPD4	NM_001368395.3		c.2035G>A	p.Ala679Thr	missense	Exon 17 of 19	NP_001355324.1
	FRMPD4	NM_001368396.3		c.1930G>A	p.Ala644Thr	missense	Exon 15 of 17	NP_001355325.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD4	ENST00000675598.1	MANE Select	c.1924G>A	p.Ala642Thr	missense	Exon 15 of 17	ENSP00000502607.1
	FRMPD4	ENST00000380682.5	TSL:1	c.1924G>A	p.Ala642Thr	missense	Exon 15 of 17	ENSP00000370057.1
	FRMPD4	ENST00000656302.1		c.1978G>A	p.Ala660Thr	missense	Exon 17 of 19	ENSP00000499481.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 30, 2016

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.7
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.095
Sift	Benign	0.29	T
Sift4G	Benign	0.45	T
Polyphen		0.0010	B
Vest4		0.093
MutPred		0.083		Gain of phosphorylation at A642 (P = 0.0514)
MVP		0.25
MPC		0.12
ClinPred		0.46	T
GERP RS		5.0
Varity_R		0.15
gMVP		0.23
Mutation Taster		=90/10	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: rs1555897781; hg19: chrX-12734502;