X-12704002-A-G

Position:

• chrX-12704002-A-G

Variant summary

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

The NM_001368397.1(FRMPD4):​c.1071-357A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 110,761 control chromosomes in the GnomAD database, including 7,789 homozygotes. There are 14,832 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 0.44 (7789 hom., 14832 hem., cov: 23)
• Consequence: FRMPD4 NM_001368397.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.711

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMPD4	NM_001368397.1	c.1071-357A>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.1071-357A>G		intron_variant			NM_001368397.1	ENSP00000502607.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 48746 AN: 110705 Hom.: 7783 Cov.: 23 AF XY: 0.449 AC XY: 14790 AN XY: 32945

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.441 AC: 48791 AN: 110761 Hom.: 7789 Cov.: 23 AF XY: 0.449 AC XY: 14832 AN XY: 33011

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.626

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.448

Alfa AF: 0.402 Hom.: 24543

Bravo AF: 0.452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.0
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4240151; hg19: chrX-12722121;