rs860759

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

FRMPD4 Gene-Disease associations (from GenCC):

• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, X-linked 104

  Inheritance: XL Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001368395.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD4	NM_001368395.3		c.152+120737G>T		intron	N/A	NP_001355324.1
	FRMPD4	NM_001368398.3		c.152+120737G>T		intron	N/A	NP_001355327.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD4	ENST00000656302.1		c.95+120737G>T		intron	N/A	ENSP00000499481.1	A0A590UJL7
	FRMPD4	ENST00000640291.2	TSL:5	c.95+120737G>T		intron	N/A	ENSP00000492353.2	A0A1W2PQW0
	FRMPD4	ENST00000672869.2		c.95+120737G>T		intron	N/A	ENSP00000500566.2	A0A5F9ZHT2

Frequencies

GnomAD3 genomes AF: 0.0920 AC: 10238 AN: 111223 Hom.: 489 Cov.: 23

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

African (AFR) AF: 0.166 AC: 5076 AN: 30540

American (AMR) AF: 0.0481 AC: 507 AN: 10534

Ashkenazi Jewish (ASJ) AF: 0.0445 AC: 117 AN: 2629

East Asian (EAS) AF: 0.00140 AC: 5 AN: 3574

South Asian (SAS) AF: 0.0398 AC: 106 AN: 2664

European-Finnish (FIN) AF: 0.0720 AC: 428 AN: 5945

Middle Eastern (MID) AF: 0.0694 AC: 15 AN: 216

European-Non Finnish (NFE) AF: 0.0722 AC: 3824 AN: 52979

Other (OTH) AF: 0.0726 AC: 110 AN: 1515

Alfa AF: 0.0786 Hom.: 2588

Bravo AF: 0.0944

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs860759; hg19: chrX-12016874;