X-12498685-G-T

Position:

• chrX-12498685-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001368397.1(FRMPD4):​c.47G>T​(p.Arg16Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: FRMPD4 NM_001368397.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.73

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.744

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMPD4	NM_001368397.1	c.47G>T	p.Arg16Met	missense_variant	2/17	ENST00000675598.1	NP_001355326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMPD4	ENST00000675598.1	c.47G>T	p.Arg16Met	missense_variant	2/17		NM_001368397.1	ENSP00000502607	P2

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1041997 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 322423

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.029	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.29	D
MetaRNN	Pathogenic	0.74	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	0.81	D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.18
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.050	T
Polyphen		1.0	D
Vest4		0.61
MutPred		0.58		Loss of MoRF binding (P = 0.0637);
MVP		0.65
MPC		2.0
ClinPred		0.92	D
GERP RS		5.1
Varity_R		0.16
gMVP		0.50

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-12516804;