Genetic Variant FRMPD4:c.1287+17_1287+26dupTTTTTTTTTT (chrX-12706923-C-CTTTTTTTTTT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001368395.3(FRMPD4):c.1398+17_1398+26dupTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000012 ( 0 hom., 0 hem., cov: 10)

Exomes 𝑓: 0.000021 ( 0 hom. 0 hem. )

Consequence

FRMPD4
NM_001368395.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.738

Publications

1 publications found

Variant links:

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

FRMPD4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FRMPD4	NM_001368397.1	MANE Select	c.1287+17_1287+26dupTTTTTTTTTT	intron	N/A	NP_001355326.1
FRMPD4	NM_001368395.3		c.1398+17_1398+26dupTTTTTTTTTT	intron	N/A	NP_001355324.1
FRMPD4	NM_001368396.3		c.1293+17_1293+26dupTTTTTTTTTT	intron	N/A	NP_001355325.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.0000122

AC:

AN:

82297

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000209

AC:

AN:

526961

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

154455

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

13072

American (AMR)

AF:

0.00

AC:

AN:

19406

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12513

East Asian (EAS)

AF:

0.0000407

AC:

AN:

24564

South Asian (SAS)

AF:

0.0000355

AC:

AN:

28176

European-Finnish (FIN)

AF:

0.0000960

AC:

AN:

31247

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2123

European-Non Finnish (NFE)

AF:

0.0000162

AC:

AN:

370156

Other (OTH)

AF:

0.00

AC:

AN:

25704

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000132589), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.361

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000122

AC:

AN:

82297

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

17461

show subpopulations

African (AFR)

AF:

0.0000447

AC:

AN:

22362

American (AMR)

AF:

0.00

AC:

AN:

7117

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2112

East Asian (EAS)

AF:

0.00

AC:

AN:

2628

South Asian (SAS)

AF:

0.00

AC:

AN:

1547

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2172

Middle Eastern (MID)

AF:

0.00

AC:

AN:

178

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

42555

Other (OTH)

AF:

0.00

AC:

AN:

1067

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Publications

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X-12706923-CTTTTTTTTT-CTTTTTTTTTTTTTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over