Genetic Variant FRMPD4:c.1287+25_1287+26dupTT (chrX-12706923-C-CTT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001368397.1(FRMPD4):c.1287+25_1287+26dupTT 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 0.022 ( 48 hom., 192 hem., cov: 10)

Exomes 𝑓: 0.0077 ( 1 hom. 10 hem. )

Consequence

FRMPD4
NM_001368397.1 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

FRMPD4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FRMPD4	NM_001368397.1	MANE Select	c.1287+25_1287+26dupTT	intron	N/A	NP_001355326.1	A0A6Q8PH73
FRMPD4	NM_001368395.3		c.1398+25_1398+26dupTT	intron	N/A	NP_001355324.1
FRMPD4	NM_001368396.3		c.1293+25_1293+26dupTT	intron	N/A	NP_001355325.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FRMPD4	ENST00000675598.1	MANE Select	c.1287+8_1287+9insTT	intron	N/A	ENSP00000502607.1	A0A6Q8PH73
FRMPD4	ENST00000380682.5	TSL:1	c.1287+8_1287+9insTT	intron	N/A	ENSP00000370057.1	Q14CM0
FRMPD4	ENST00000656302.1		c.1341+8_1341+9insTT	intron	N/A	ENSP00000499481.1	A0A590UJL7

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

1795

AN:

82185

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0615

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0390

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0290

Gnomad SAS

AF:

0.000647

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00562

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.0243

GnomAD2 exomes

AF:

0.00924

AC:

477

AN:

51637

AF XY:

0.00155

show subpopulations

Gnomad AFR exome

AF:

0.0160

Gnomad AMR exome

AF:

0.0181

Gnomad ASJ exome

AF:

0.00622

Gnomad EAS exome

AF:

0.0122

Gnomad FIN exome

AF:

0.00502

Gnomad NFE exome

AF:

0.00633

Gnomad OTH exome

AF:

0.00746

GnomAD4 exome

AF:

0.00770

AC:

4005

AN:

520195

Hom.:

Cov.:

AF XY:

0.0000668

AC XY:

AN XY:

149597

show subpopulations

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

African (AFR)

AF:

0.0240

AC:

306

AN:

12766

American (AMR)

AF:

0.0159

AC:

305

AN:

19140

Ashkenazi Jewish (ASJ)

AF:

0.00507

AC:

AN:

12426

East Asian (EAS)

AF:

0.0146

AC:

352

AN:

24151

South Asian (SAS)

AF:

0.00433

AC:

120

AN:

27686

European-Finnish (FIN)

AF:

0.00495

AC:

153

AN:

30930

Middle Eastern (MID)

AF:

0.00762

AC:

AN:

2101

European-Non Finnish (NFE)

AF:

0.00677

AC:

2477

AN:

365649

Other (OTH)

AF:

0.00840

AC:

213

AN:

25346

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.308

Heterozygous variant carriers

309

618

928

1237

1546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<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:

0.0218

AC:

1795

AN:

82169

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

192

AN XY:

17397

show subpopulations

African (AFR)

AF:

0.0614

AC:

1371

AN:

22318

American (AMR)

AF:

0.0391

AC:

278

AN:

7109

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2110

East Asian (EAS)

AF:

0.0288

AC:

AN:

2608

South Asian (SAS)

AF:

0.000651

AC:

AN:

1535

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2170

Middle Eastern (MID)

AF:

0.00617

AC:

AN:

162

European-Non Finnish (NFE)

AF:

0.00101

AC:

AN:

42517

Other (OTH)

AF:

0.0241

AC:

AN:

1081

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

120

179

239

299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

295

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.74

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over