NM_001368397.1:c.1071-357A>G

Variant names:

• chrX-12704002-A-G
• rs4240151
• NM_001368397.1:c.1071-357A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001368397.1(FRMPD4):​c.1071-357A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 110,761 control chromosomes in the GnomAD database, including 7,789 homozygotes. There are 14,832 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (7789 hom., 14832 hem., cov: 23)
• Consequence: FRMPD4 NM_001368397.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.711
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD4	NM_001368397.1	MANE Select	c.1071-357A>G		intron	N/A	NP_001355326.1
	FRMPD4	NM_001368395.3		c.1182-357A>G		intron	N/A	NP_001355324.1
	FRMPD4	NM_001368396.3		c.1077-357A>G		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.1071-357A>G		intron	N/A	ENSP00000502607.1
	FRMPD4	ENST00000380682.5	TSL:1	c.1071-357A>G		intron	N/A	ENSP00000370057.1
	FRMPD4	ENST00000656302.1		c.1125-357A>G		intron	N/A	ENSP00000499481.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 48746 AN: 110705 Hom.: 7783 Cov.: 23

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.444

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.441 AC: 48791 AN: 110761 Hom.: 7789 Cov.: 23 AF XY: 0.449 AC XY: 14832 AN XY: 33011

African (AFR) AF: 0.465 AC: 14144 AN: 30422

American (AMR) AF: 0.562 AC: 5871 AN: 10455

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 839 AN: 2640

East Asian (EAS) AF: 0.819 AC: 2863 AN: 3494

South Asian (SAS) AF: 0.626 AC: 1613 AN: 2575

European-Finnish (FIN) AF: 0.482 AC: 2847 AN: 5908

Middle Eastern (MID) AF: 0.428 AC: 92 AN: 215

European-Non Finnish (NFE) AF: 0.373 AC: 19691 AN: 52855

Other (OTH) AF: 0.448 AC: 681 AN: 1520

Alfa AF: 0.410 Hom.: 35924

Bravo AF: 0.452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.0
DANN	Benign	0.80
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs4240151; hg19: chrX-12722121;