X-12718639-C-T

Variant names:

• chrX-12718639-C-T
• rs376423451
• NM_001368397.1:c.3813C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001368397.1(FRMPD4):​c.3813C>T​(p.His1271His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,208,156 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 71 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., 7 hem., cov: 23)
  • Exomes 𝑓: 0.00014 (0 hom. 64 hem.)
• Consequence: FRMPD4 NM_001368397.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.684
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-12718639-C-T is Benign according to our data. Variant chrX-12718639-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 435269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.684 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 7 XL gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD4	NM_001368397.1	MANE Select	c.3813C>T	p.His1271His	synonymous	Exon 16 of 17	NP_001355326.1
	FRMPD4	NM_001368395.3		c.3924C>T	p.His1308His	synonymous	Exon 18 of 19	NP_001355324.1
	FRMPD4	NM_001368396.3		c.3819C>T	p.His1273His	synonymous	Exon 16 of 17	NP_001355325.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD4	ENST00000675598.1	MANE Select	c.3813C>T	p.His1271His	synonymous	Exon 16 of 17	ENSP00000502607.1
	FRMPD4	ENST00000380682.5	TSL:1	c.3813C>T	p.His1271His	synonymous	Exon 16 of 17	ENSP00000370057.1
	FRMPD4	ENST00000656302.1		c.3867C>T	p.His1289His	synonymous	Exon 18 of 19	ENSP00000499481.1

Frequencies

GnomAD3 genomes AF: 0.000152 AC: 17 AN: 112011 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000376

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000282

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000158 AC: 29 AN: 183253 AF XY: 0.000236

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000183

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000138 AC: 151 AN: 1096093 Hom.: 0 Cov.: 31 AF XY: 0.000177 AC XY: 64 AN XY: 361489

African (AFR) AF: 0.00 AC: 0 AN: 26355

American (AMR) AF: 0.0000284 AC: 1 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19372

East Asian (EAS) AF: 0.00 AC: 0 AN: 30199

South Asian (SAS) AF: 0.000721 AC: 39 AN: 54109

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40508

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4130

European-Non Finnish (NFE) AF: 0.000126 AC: 106 AN: 840190

Other (OTH) AF: 0.0000869 AC: 4 AN: 46025

GnomAD4 genome AF: 0.000152 AC: 17 AN: 112063 Hom.: 0 Cov.: 23 AF XY: 0.000205 AC XY: 7 AN XY: 34225

African (AFR) AF: 0.0000324 AC: 1 AN: 30858

American (AMR) AF: 0.00 AC: 0 AN: 10623

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3552

South Asian (SAS) AF: 0.000378 AC: 1 AN: 2649

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6125

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.000282 AC: 15 AN: 53164

Other (OTH) AF: 0.00 AC: 0 AN: 1538

Alfa AF: 0.000218 Hom.: 3

Bravo AF: 0.000136

EpiCase AF: 0.000545

EpiControl AF: 0.000356

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Aug 04, 2017

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FRMPD4: BP4, BP7, BS2

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.040
DANN	Benign	0.32
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism

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: rs376423451; hg19: chrX-12736758;