rs860759

Variant names:

• chrX-11998755-G-T
• rs860759
• NM_001368395.3:c.152+120737G>T

Variant summary

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

The NM_001368395.3(FRMPD4):​c.152+120737G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 111,274 control chromosomes in the GnomAD database, including 488 homozygotes. There are 2,806 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 0.092 (488 hom., 2806 hem., cov: 23)
• Consequence: FRMPD4 NM_001368395.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD4	NM_001368395.3	c.152+120737G>T		intron_variant	Intron 3 of 18		NP_001355324.1
FRMPD4	NM_001368398.3	c.152+120737G>T		intron_variant	Intron 3 of 18		NP_001355327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD4	ENST00000656302.1	c.95+120737G>T		intron_variant	Intron 3 of 18			ENSP00000499481.1
FRMPD4	ENST00000640291.2	c.95+120737G>T		intron_variant	Intron 3 of 18	5		ENSP00000492353.2
FRMPD4	ENST00000672869.2	c.95+120737G>T		intron_variant	Intron 1 of 15			ENSP00000500566.2
FRMPD4	ENST00000673271.2	n.597+120737G>T		intron_variant	Intron 3 of 19

Frequencies

GnomAD3 genomes AF: 0.0920 AC: 10238 AN: 111223 Hom.: 489 Cov.: 23 AF XY: 0.0836 AC XY: 2803 AN XY: 33527

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.0723

Gnomad AMR AF: 0.0482

Gnomad ASJ AF: 0.0445

Gnomad EAS AF: 0.00139

Gnomad SAS AF: 0.0400

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.0672

Gnomad NFE AF: 0.0722

Gnomad OTH AF: 0.0735

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

GnomAD4 genome AF: 0.0920 AC: 10237 AN: 111274 Hom.: 488 Cov.: 23 AF XY: 0.0835 AC XY: 2806 AN XY: 33588

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.0481

Gnomad4 ASJ AF: 0.0445

Gnomad4 EAS AF: 0.00140

Gnomad4 SAS AF: 0.0398

Gnomad4 FIN AF: 0.0720

Gnomad4 NFE AF: 0.0722

Gnomad4 OTH AF: 0.0726

Alfa AF: 0.0773 Hom.: 1357

Bravo AF: 0.0944

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs860759; hg19: chrX-12016874;