X-12529371-A-G

Variant names:

• chrX-12529371-A-G
• rs5934013
• NM_001368397.1:c.158+30575A>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.158+30575A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 111,226 control chromosomes in the GnomAD database, including 6,904 homozygotes. There are 13,023 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 0.40 (6904 hom., 13023 hem., cov: 23)
• Consequence: FRMPD4 NM_001368397.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 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.158+30575A>G		intron	N/A	NP_001355326.1	A0A6Q8PH73
	FRMPD4	NM_001368395.3		c.269+30575A>G		intron	N/A	NP_001355324.1
	FRMPD4	NM_001368396.3		c.158+30575A>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.158+30575A>G		intron	N/A	ENSP00000502607.1	A0A6Q8PH73
	FRMPD4	ENST00000380682.5	TSL:1	c.158+30575A>G		intron	N/A	ENSP00000370057.1	Q14CM0
	FRMPD4	ENST00000656302.1		c.212+30575A>G		intron	N/A	ENSP00000499481.1	A0A590UJL7

Frequencies

GnomAD3 genomes AF: 0.401 AC: 44530 AN: 111172 Hom.: 6906 Cov.: 23

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.461

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.400 AC: 44522 AN: 111226 Hom.: 6904 Cov.: 23 AF XY: 0.389 AC XY: 13023 AN XY: 33462

African (AFR) AF: 0.230 AC: 7069 AN: 30727

American (AMR) AF: 0.384 AC: 4044 AN: 10542

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1368 AN: 2637

East Asian (EAS) AF: 0.281 AC: 986 AN: 3511

South Asian (SAS) AF: 0.324 AC: 855 AN: 2635

European-Finnish (FIN) AF: 0.459 AC: 2706 AN: 5893

Middle Eastern (MID) AF: 0.469 AC: 99 AN: 211

European-Non Finnish (NFE) AF: 0.501 AC: 26477 AN: 52882

Other (OTH) AF: 0.397 AC: 602 AN: 1515

Alfa AF: 0.459 Hom.: 55746

Bravo AF: 0.389

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.73
DANN	Benign	0.70
PhyloP100		-0.15
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

Other links and lift over

dbSNP: rs5934013; hg19: chrX-12547490;