chrX-12609725-A-G

Position:

• chrX-12609725-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001368397.1(FRMPD4):​c.163A>G​(p.Met55Val) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: FRMPD4 NM_001368397.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.88

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13956311).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMPD4	NM_001368397.1	c.163A>G	p.Met55Val	missense_variant	3/17	ENST00000675598.1	NP_001355326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMPD4	ENST00000675598.1	c.163A>G	p.Met55Val	missense_variant	3/17		NM_001368397.1	ENSP00000502607	P2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 19, 2024

The c.163A>G (p.M55V) alteration is located in exon 3 (coding exon 3) of the FRMPD4 gene. This alteration results from a A to G substitution at nucleotide position 163, causing the methionine (M) at amino acid position 55 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	15
DANN	Benign	0.70
DEOGEN2	Benign	0.023	T;T
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.28	N;.
MutationTaster	Benign	0.57	D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.010	N;.
REVEL	Benign	0.11
Sift	Benign	0.79	T;.
Sift4G	Benign	0.84	T;T
Polyphen		0.0030	B;.
Vest4		0.31
MutPred		0.45		Gain of catalytic residue at M55 (P = 0.1565);.;
MVP		0.45
MPC		0.90
ClinPred		0.67	D
GERP RS		5.4
Varity_R		0.22
gMVP		0.49

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-12627844;