X-12706923-CTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTT

Variant names:

• chrX-12706923-C-CTTTTTTTTTTTT
• rs746601138
• NM_001368397.1:c.1287+15_1287+26dupTTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001368397.1(FRMPD4):​c.1287+15_1287+26dupTTTTTTTTTTTT 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., 0 hem., cov: 10)
  • Exomes 𝑓: 0.0000057 (0 hom. 0 hem.)
• Consequence: FRMPD4 NM_001368397.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant X-12706923-C-CTTTTTTTTTTTT is Benign according to our data. Variant chrX-12706923-C-CTTTTTTTTTTTT is described in ClinVar as [Likely_benign]. Clinvar id is 789250.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD4	NM_001368397.1	c.1287+15_1287+26dupTTTTTTTTTTTT		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+8_1287+9insTTTTTTTTTTTT		intron_variant	Intron 12 of 16		NM_001368397.1	ENSP00000502607.1

Frequencies

GnomAD3 genomes AF: 0.0000365 AC: 3 AN: 82292 Hom.: 0 Cov.: 10

Gnomad AFR AF: 0.0000447

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: 0.000460

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000235

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000569 AC: 3 AN: 526962 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 154454

⚠️ 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: 0.0000515 AC: 1 AN: 19406

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 24564

South Asian (SAS) AF: 0.00 AC: 0 AN: 28176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31246

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

European-Non Finnish (NFE) AF: 0.00000540 AC: 2 AN: 370158

Other (OTH) AF: 0.00 AC: 0 AN: 25704

⚠️ 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 AF: 0.0000365 AC: 3 AN: 82276 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 17454

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

African (AFR) AF: 0.0000447 AC: 1 AN: 22376

American (AMR) AF: 0.00 AC: 0 AN: 7115

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2111

East Asian (EAS) AF: 0.00 AC: 0 AN: 2616

South Asian (SAS) AF: 0.00 AC: 0 AN: 1536

European-Finnish (FIN) AF: 0.000460 AC: 1 AN: 2172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 162

European-Non Finnish (NFE) AF: 0.0000235 AC: 1 AN: 42550

Other (OTH) AF: 0.00 AC: 0 AN: 1079

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000489 Hom.: 295

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 09, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

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;