X-12529371-A-G

Variant names:

• chrX-12529371-A-G
• rs5934013
• NM_001368397.1:c.158+30575A>G

Variant summary

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

The NM_001368397.1(FRMPD4):​c.158+30575A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 111,226 control chromosomes in the GnomAD database, including 6,904 homozygotes. There are 13,023 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 0.40 (6904 hom., 13023 hem., cov: 23)
• Consequence: FRMPD4 NM_001368397.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD4	NM_001368397.1	c.158+30575A>G		intron_variant	Intron 2 of 16	ENST00000675598.1	NP_001355326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD4	ENST00000675598.1	c.158+30575A>G		intron_variant	Intron 2 of 16		NM_001368397.1	ENSP00000502607.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 44530 AN: 111172 Hom.: 6906 Cov.: 23 AF XY: 0.390 AC XY: 13015 AN XY: 33398

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.461

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.400 AC: 44522 AN: 111226 Hom.: 6904 Cov.: 23 AF XY: 0.389 AC XY: 13023 AN XY: 33462

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.397

Alfa AF: 0.481 Hom.: 44197

Bravo AF: 0.389

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.73
DANN	Benign	0.70

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: rs5934013; hg19: chrX-12547490;