X-12157756-T-G

Position:

• chrX-12157756-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001368397.1(FRMPD4):​c.41+18744T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0785 in 112,194 control chromosomes in the GnomAD database, including 967 homozygotes. There are 3,006 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.078 (967 hom., 3006 hem., cov: 24)
• Consequence: FRMPD4 NM_001368397.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.265

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMPD4	NM_001368397.1	c.41+18744T>G		intron_variant		ENST00000675598.1	NP_001355326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMPD4	ENST00000675598.1	c.41+18744T>G		intron_variant			NM_001368397.1	ENSP00000502607	P2

Frequencies

GnomAD3 genomes AF: 0.0785 AC: 8798 AN: 112139 Hom.: 970 Cov.: 24 AF XY: 0.0873 AC XY: 2994 AN XY: 34291

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.00730

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0526

Gnomad MID AF: 0.0798

Gnomad NFE AF: 0.0267

Gnomad OTH AF: 0.0987

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0785 AC: 8804 AN: 112194 Hom.: 967 Cov.: 24 AF XY: 0.0875 AC XY: 3006 AN XY: 34356

Gnomad4 AFR AF: 0.0254

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.0490

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.0526

Gnomad4 NFE AF: 0.0267

Gnomad4 OTH AF: 0.0993

Alfa AF: 0.0624 Hom.: 407

Bravo AF: 0.105

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.38

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: rs10521622; hg19: chrX-12175875;