rs376423451

Variant names:

• chrX-12718639-C-G
• rs376423451
• NM_001368397.1:c.3813C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-12718639-C-G
• chrX-12718639-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001368397.1(FRMPD4):​c.3813C>G​(p.His1271Gln) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H1271H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: FRMPD4 NM_001368397.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.684
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039897352).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD4	NM_001368397.1	c.3813C>G	p.His1271Gln	missense_variant	Exon 16 of 17	ENST00000675598.1	NP_001355326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD4	ENST00000675598.1	c.3813C>G	p.His1271Gln	missense_variant	Exon 16 of 17		NM_001368397.1	ENSP00000502607.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.011
DANN	Benign	0.73
DEOGEN2	Benign	0.022	T;T
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.040	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.76	N;.
PhyloP100		-0.68
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.070	N;.
REVEL	Benign	0.053
Sift	Benign	0.49	T;.
Sift4G	Benign	0.48	T;T
Polyphen		0.042	B;.
Vest4		0.19
MutPred		0.13		Gain of disorder (P = 0.2123);.;
MVP		0.13
MPC		0.13
ClinPred		0.11	T
GERP RS		-7.4
Varity_R		0.041
gMVP		0.34
Mutation Taster		=96/4	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: rs376423451; hg19: chrX-12736758;