X-12157756-T-G

Variant names:

• chrX-12157756-T-G
• rs10521622
• NM_001368397.1:c.41+18744T>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.41+18744T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0785 in 112,194 control chromosomes in the GnomAD database, including 967 homozygotes. There are 3,006 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 0.078 (967 hom., 3006 hem., cov: 24)
• Consequence: FRMPD4 NM_001368397.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.265
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD4	NM_001368397.1	c.41+18744T>G		intron_variant	Intron 1 of 16	ENST00000675598.1	NP_001355326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD4	ENST00000675598.1	c.41+18744T>G		intron_variant	Intron 1 of 16		NM_001368397.1	ENSP00000502607.1

Frequencies

GnomAD3 genomes AF: 0.0785 AC: 8798 AN: 112139 Hom.: 970 Cov.: 24

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.00730

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0526

Gnomad MID AF: 0.0798

Gnomad NFE AF: 0.0267

Gnomad OTH AF: 0.0987

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

GnomAD4 genome AF: 0.0785 AC: 8804 AN: 112194 Hom.: 967 Cov.: 24 AF XY: 0.0875 AC XY: 3006 AN XY: 34356

African (AFR) AF: 0.0254 AC: 787 AN: 30948

American (AMR) AF: 0.292 AC: 3077 AN: 10549

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 130 AN: 2651

East Asian (EAS) AF: 0.650 AC: 2276 AN: 3503

South Asian (SAS) AF: 0.227 AC: 609 AN: 2682

European-Finnish (FIN) AF: 0.0526 AC: 325 AN: 6184

Middle Eastern (MID) AF: 0.0922 AC: 20 AN: 217

European-Non Finnish (NFE) AF: 0.0267 AC: 1423 AN: 53245

Other (OTH) AF: 0.0993 AC: 152 AN: 1530

Alfa AF: 0.0624 Hom.: 407

Bravo AF: 0.105

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.38
PhyloP100		0.27
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: rs10521622; hg19: chrX-12175875;