NM_001368397.1:c.1287+16_1287+26dupTTTTTTTTTTT

Variant names:

• chrX-12706923-C-CTTTTTTTTTTT
• rs746601138
• NM_001368397.1:c.1287+16_1287+26dupTTTTTTTTTTT

Variant summary

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

The NM_001368397.1(FRMPD4):​c.1287+16_1287+26dupTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000061 (0 hom., 0 hem., cov: 10)
  • Exomes 𝑓: 0.000028 (0 hom. 0 hem.)
• Consequence: FRMPD4 NM_001368397.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.738
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001368397.1. 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_001368397.1	MANE Select	c.1287+16_1287+26dupTTTTTTTTTTT		intron	N/A	NP_001355326.1
	FRMPD4	NM_001368395.3		c.1398+16_1398+26dupTTTTTTTTTTT		intron	N/A	NP_001355324.1
	FRMPD4	NM_001368396.3		c.1293+16_1293+26dupTTTTTTTTTTT		intron	N/A	NP_001355325.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD4	ENST00000675598.1	MANE Select	c.1287+8_1287+9insTTTTTTTTTTT		intron	N/A	ENSP00000502607.1
	FRMPD4	ENST00000380682.5	TSL:1	c.1287+8_1287+9insTTTTTTTTTTT		intron	N/A	ENSP00000370057.1
	FRMPD4	ENST00000656302.1		c.1341+8_1341+9insTTTTTTTTTTT		intron	N/A	ENSP00000499481.1

Frequencies

GnomAD3 genomes AF: 0.0000608 AC: 5 AN: 82291 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: 0.000118

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000285 AC: 15 AN: 526955 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 154451

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

African (AFR) AF: 0.00 AC: 0 AN: 13072

American (AMR) AF: 0.00 AC: 0 AN: 19404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12513

East Asian (EAS) AF: 0.0000407 AC: 1 AN: 24564

South Asian (SAS) AF: 0.0000710 AC: 2 AN: 28174

European-Finnish (FIN) AF: 0.0000640 AC: 2 AN: 31247

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2123

European-Non Finnish (NFE) AF: 0.0000243 AC: 9 AN: 370155

Other (OTH) AF: 0.0000389 AC: 1 AN: 25703

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000630350), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000608 AC: 5 AN: 82291 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 17459

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

African (AFR) AF: 0.00 AC: 0 AN: 22361

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: 0.000118 AC: 5 AN: 42550

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000929732), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000978 Hom.: 295

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.74

Splicing

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

Other links and lift over

dbSNP: rs746601138; hg19: chrX-12725042;