X-12723383-T-G

Variant names:

• chrX-12723383-T-G
• rs5979717
• NM_001368397.1:c.*1525T>G

Variant summary

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

The NM_001368397.1(FRMPD4):​c.*1525T>G variant causes a 3 prime UTR 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 0.63 (16184 hom., 19782 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: FRMPD4 NM_001368397.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 5 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

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.*1525T>G		3_prime_UTR	Exon 17 of 17	NP_001355326.1	A0A6Q8PH73
	FRMPD4	NM_001368395.3		c.*1525T>G		3_prime_UTR	Exon 19 of 19	NP_001355324.1
	FRMPD4	NM_001368396.3		c.*1525T>G		3_prime_UTR	Exon 17 of 17	NP_001355325.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD4	ENST00000675598.1	MANE Select	c.*1525T>G		3_prime_UTR	Exon 17 of 17	ENSP00000502607.1	A0A6Q8PH73
	FRMPD4	ENST00000380682.5	TSL:1	c.*2850T>G		3_prime_UTR	Exon 17 of 17	ENSP00000370057.1	Q14CM0
	FRMPD4	ENST00000672010.1		c.*2850T>G		3_prime_UTR	Exon 17 of 17	ENSP00000499962.1	A0A5F9ZH12

Frequencies

GnomAD3 genomes AF: 0.633 AC: 69356 AN: 109550 Hom.: 16190 Cov.: 22

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.625

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.633 AC: 69378 AN: 109597 Hom.: 16184 Cov.: 22 AF XY: 0.620 AC XY: 19782 AN XY: 31901

African (AFR) AF: 0.762 AC: 22969 AN: 30124

American (AMR) AF: 0.579 AC: 5945 AN: 10272

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 1740 AN: 2622

East Asian (EAS) AF: 0.726 AC: 2534 AN: 3488

South Asian (SAS) AF: 0.427 AC: 1083 AN: 2536

European-Finnish (FIN) AF: 0.491 AC: 2785 AN: 5675

Middle Eastern (MID) AF: 0.659 AC: 141 AN: 214

European-Non Finnish (NFE) AF: 0.587 AC: 30821 AN: 52503

Other (OTH) AF: 0.623 AC: 928 AN: 1490

Alfa AF: 0.618 Hom.: 5995

Bravo AF: 0.648

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.46
PhyloP100		-0.076
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: rs5979717; hg19: chrX-12741502;