X-12182662-C-T

Variant names:

• chrX-12182662-C-T
• rs6530488
• NM_001368397.1:c.41+43650C>T

Variant summary

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

The NM_001368397.1(FRMPD4):​c.41+43650C>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 0.78 (24128 hom., 24200 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: FRMPD4 NM_001368397.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 0 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=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD4	NM_001368397.1	c.41+43650C>T		intron_variant	Intron 1 of 16	ENST00000675598.1	NP_001355326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD4	ENST00000675598.1	c.41+43650C>T		intron_variant	Intron 1 of 16		NM_001368397.1	ENSP00000502607.1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 84895 AN: 108420 Hom.: 24127 Cov.: 21

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.766

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: 0.783 AC: 84932 AN: 108455 Hom.: 24128 Cov.: 21 AF XY: 0.784 AC XY: 24200 AN XY: 30871

African (AFR) AF: 0.897 AC: 26723 AN: 29795

American (AMR) AF: 0.830 AC: 8332 AN: 10035

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 1800 AN: 2604

East Asian (EAS) AF: 0.970 AC: 3338 AN: 3440

South Asian (SAS) AF: 0.830 AC: 2047 AN: 2465

European-Finnish (FIN) AF: 0.727 AC: 3912 AN: 5378

Middle Eastern (MID) AF: 0.696 AC: 149 AN: 214

European-Non Finnish (NFE) AF: 0.705 AC: 36940 AN: 52371

Other (OTH) AF: 0.769 AC: 1143 AN: 1487

Alfa AF: 0.738 Hom.: 108217

Bravo AF: 0.799

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.67
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6530488; hg19: chrX-12200781;