X-11864438-C-T

Variant names:

• chrX-11864438-C-T
• rs1534285
• NM_001368395.3:c.-103-648C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001368395.3(FRMPD4):​c.-103-648C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.63 (15335 hom., 19341 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: FRMPD4 NM_001368395.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 1 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Illumina
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

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.-103-648C>T		intron	N/A	NP_001355324.1
	FRMPD4	NM_001368398.3		c.-103-648C>T		intron	N/A	NP_001355327.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD4	ENST00000656302.1		c.-160-648C>T		intron	N/A	ENSP00000499481.1
	FRMPD4	ENST00000640291.2	TSL:5	c.-160-648C>T		intron	N/A	ENSP00000492353.2
	FRMPD4	ENST00000673271.2		n.275-648C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.629 AC: 67951 AN: 108044 Hom.: 15345 Cov.: 21

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.650

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.629 AC: 67976 AN: 108099 Hom.: 15335 Cov.: 21 AF XY: 0.634 AC XY: 19341 AN XY: 30513

African (AFR) AF: 0.654 AC: 19439 AN: 29710

American (AMR) AF: 0.638 AC: 6353 AN: 9963

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 1830 AN: 2601

East Asian (EAS) AF: 0.426 AC: 1417 AN: 3329

South Asian (SAS) AF: 0.522 AC: 1292 AN: 2474

European-Finnish (FIN) AF: 0.661 AC: 3559 AN: 5385

Middle Eastern (MID) AF: 0.681 AC: 143 AN: 210

European-Non Finnish (NFE) AF: 0.625 AC: 32676 AN: 52285

Other (OTH) AF: 0.645 AC: 959 AN: 1486

Alfa AF: 0.628 Hom.: 8064

Bravo AF: 0.629

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.32
DANN	Benign	0.48
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs1534285; hg19: chrX-11882557;