Genetic Variant FRMPD4:c.1287+18_1287+26delTTTTTTTTT (chrX-12706923-CTTTTTTTTT-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001368395.3(FRMPD4):c.1398+18_1398+26delTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 609,242 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000024 ( 0 hom., 2 hem., cov: 10)

Exomes 𝑓: 0.000017 ( 0 hom. 3 hem. )

Consequence

FRMPD4
NM_001368395.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.48

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: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

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+18_1287+26delTTTTTTTTT	intron	N/A	NP_001355326.1
FRMPD4	NM_001368395.3		c.1398+18_1398+26delTTTTTTTTT	intron	N/A	NP_001355324.1
FRMPD4	NM_001368396.3		c.1293+18_1293+26delTTTTTTTTT	intron	N/A	NP_001355325.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FRMPD4	ENST00000675598.1	MANE Select	c.1287+9_1287+17delTTTTTTTTT	intron	N/A	ENSP00000502607.1
FRMPD4	ENST00000380682.5	TSL:1	c.1287+9_1287+17delTTTTTTTTT	intron	N/A	ENSP00000370057.1
FRMPD4	ENST00000656302.1		c.1341+9_1341+17delTTTTTTTTT	intron	N/A	ENSP00000499481.1

Frequencies

GnomAD3 genomes

AF:

0.0000243

AC:

AN:

82297

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000281

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:

0.0000171

AC:

AN:

526960

Hom.:

AF XY:

0.0000194

AC XY:

AN XY:

154452

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13072

American (AMR)

AF:

0.000412

AC:

AN:

19406

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12513

East Asian (EAS)

AF:

0.00

AC:

AN:

24564

South Asian (SAS)

AF:

0.00

AC:

AN:

28175

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31247

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2123

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

370156

Other (OTH)

AF:

0.00

AC:

AN:

25704

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000243

AC:

AN:

82282

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

17456

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22378

American (AMR)

AF:

0.000281

AC:

AN:

7120

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2112

East Asian (EAS)

AF:

0.00

AC:

AN:

2616

South Asian (SAS)

AF:

0.00

AC:

AN:

1536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2172

Middle Eastern (MID)

AF:

0.00

AC:

AN:

162

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

42548

Other (OTH)

AF:

0.00

AC:

AN:

1079

Alfa

AF:

0.00

Hom.:

295

Bravo

AF:

0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

Splicing

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

Publications

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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