X-12609792-G-A

Position:

• chrX-12609792-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001368397.1(FRMPD4):​c.230G>A​(p.Arg77Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000365 in 1,095,450 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000037 (0 hom. 2 hem.)
• Consequence: FRMPD4 NM_001368397.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.37

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMPD4	NM_001368397.1	c.230G>A	p.Arg77Gln	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.230G>A	p.Arg77Gln	missense_variant	3/17		NM_001368397.1	ENSP00000502607	P2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000545 AC: 1 AN: 183409 Hom.: 0 AF XY: 0.0000147 AC XY: 1 AN XY: 67863

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.00000365 AC: 4 AN: 1095450 Hom.: 0 Cov.: 29 AF XY: 0.00000554 AC XY: 2 AN XY: 360866

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000284

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: 0.00000357

Gnomad4 OTH exome AF: 0.00

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

Oct 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.37	T;T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Pathogenic	0.37	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M;.
MutationTaster	Benign	0.98	D
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.7	D;.
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.039	D;T
Polyphen		1.0	D;.
Vest4		0.82
MutPred		0.60		Gain of ubiquitination at K78 (P = 0.0435);.;
MVP		0.81
MPC		2.2
ClinPred		0.95	D
GERP RS		4.4
Varity_R		0.66
gMVP		0.80

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

LitVar

Other links and lift over

dbSNP: rs1166072644; hg19: chrX-12627911;