NM_001368397.1:c.1287+23_1287+26delTTTT

Variant names:

• chrX-12706923-CTTTT-C
• rs746601138
• NM_001368397.1:c.1287+23_1287+26delTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001368397.1(FRMPD4):​c.1287+23_1287+26delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 518,919 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 10)
  • Exomes 𝑓: 0.0027 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: FRMPD4 NM_001368397.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD4	NM_001368397.1	c.1287+23_1287+26delTTTT		intron_variant	Intron 12 of 16	ENST00000675598.1	NP_001355326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD4	ENST00000675598.1	c.1287+9_1287+12delTTTT		intron_variant	Intron 12 of 16		NM_001368397.1	ENSP00000502607.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 82295 Hom.: 0 Cov.: 10

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00270 AC: 1402 AN: 518919 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 150345

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00302 AC: 39 AN: 12911

American (AMR) AF: 0.00350 AC: 67 AN: 19124

Ashkenazi Jewish (ASJ) AF: 0.00309 AC: 38 AN: 12313

East Asian (EAS) AF: 0.00174 AC: 42 AN: 24150

South Asian (SAS) AF: 0.00302 AC: 83 AN: 27459

European-Finnish (FIN) AF: 0.00140 AC: 43 AN: 30814

Middle Eastern (MID) AF: 0.000956 AC: 2 AN: 2093

European-Non Finnish (NFE) AF: 0.00282 AC: 1030 AN: 364730

Other (OTH) AF: 0.00229 AC: 58 AN: 25325

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 82295 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 17459

African (AFR) AF: 0.00 AC: 0 AN: 22362

American (AMR) AF: 0.00 AC: 0 AN: 7117

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2112

East Asian (EAS) AF: 0.00 AC: 0 AN: 2628

South Asian (SAS) AF: 0.00 AC: 0 AN: 1547

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 178

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 42553

Other (OTH) AF: 0.00 AC: 0 AN: 1067

Alfa AF: 0.00240 Hom.: 295

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs746601138; hg19: chrX-12725042;