X-12425940-G-A

Variant names:

• chrX-12425940-G-A
• rs2407843
• NM_001368397.1:c.42-72740G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001368397.1(FRMPD4):​c.42-72740G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.61 (15050 hom., 19927 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: FRMPD4 NM_001368397.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188
• 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: G2P, Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

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.42-72740G>A		intron	N/A	NP_001355326.1	A0A6Q8PH73
	FRMPD4	NM_001368395.3		c.153-72740G>A		intron	N/A	NP_001355324.1
	FRMPD4	NM_001368396.3		c.42-72740G>A		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.42-72740G>A		intron	N/A	ENSP00000502607.1	A0A6Q8PH73
	FRMPD4	ENST00000380682.5	TSL:1	c.42-72740G>A		intron	N/A	ENSP00000370057.1	Q14CM0
	FRMPD4	ENST00000656302.1		c.96-72740G>A		intron	N/A	ENSP00000499481.1	A0A590UJL7

Frequencies

GnomAD3 genomes AF: 0.610 AC: 67403 AN: 110450 Hom.: 15054 Cov.: 22

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.638

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.629

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.610 AC: 67431 AN: 110507 Hom.: 15050 Cov.: 22 AF XY: 0.608 AC XY: 19927 AN XY: 32759

African (AFR) AF: 0.440 AC: 13372 AN: 30413

American (AMR) AF: 0.646 AC: 6757 AN: 10465

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 1898 AN: 2618

East Asian (EAS) AF: 0.749 AC: 2609 AN: 3482

South Asian (SAS) AF: 0.867 AC: 2213 AN: 2552

European-Finnish (FIN) AF: 0.665 AC: 3853 AN: 5797

Middle Eastern (MID) AF: 0.626 AC: 132 AN: 211

European-Non Finnish (NFE) AF: 0.667 AC: 35226 AN: 52776

Other (OTH) AF: 0.634 AC: 960 AN: 1515

Alfa AF: 0.664 Hom.: 56086

Bravo AF: 0.603

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.59
DANN	Benign	0.64
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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.

Other links and lift over

dbSNP: rs2407843;

hg19: chrX-12444059;