X-12498716-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001368397.1(FRMPD4):c.78G>A(p.Ser26=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000367 in 1,196,754 control chromosomes in the GnomAD database, including 3 homozygotes. There are 101 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., 41 hem., cov: 21)
  • Exomes 𝑓: 0.00022 (1 hom. 60 hem.)
• Consequence: FRMPD4 NM_001368397.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.80

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant X-12498716-G-A is Benign according to our data. Variant chrX-12498716-G-A is described in ClinVar as [Benign]. Clinvar id is 735550.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.8 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMPD4	NM_001368397.1	c.78G>A	p.Ser26=	synonymous_variant	2/17	ENST00000675598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMPD4	ENST00000675598.1	c.78G>A	p.Ser26=	synonymous_variant	2/17		NM_001368397.1	P2

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 198 AN: 105479 Hom.: 2 Cov.: 21 AF XY: 0.00143 AC XY: 41 AN XY: 28691

Gnomad AFR AF: 0.00609

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00184

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000777

Gnomad OTH AF: 0.000715

GnomAD3 exomes AF: 0.000584 AC: 106 AN: 181556 Hom.: 1 AF XY: 0.000332 AC XY: 22 AN XY: 66264

Gnomad AFR exome AF: 0.00626

Gnomad AMR exome AF: 0.000624

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000536

Gnomad FIN exome AF: 0.0000628

Gnomad NFE exome AF: 0.0000494

Gnomad OTH exome AF: 0.000223

GnomAD4 exome AF: 0.000221 AC: 241 AN: 1091234 Hom.: 1 Cov.: 28 AF XY: 0.000168 AC XY: 60 AN XY: 356972

Gnomad4 AFR exome AF: 0.00594

Gnomad4 AMR exome AF: 0.000598

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000494

Gnomad4 NFE exome AF: 0.0000443

Gnomad4 OTH exome AF: 0.000545

GnomAD4 genome AF: 0.00188 AC: 198 AN: 105520 Hom.: 2 Cov.: 21 AF XY: 0.00143 AC XY: 41 AN XY: 28742

Gnomad4 AFR AF: 0.00608

Gnomad4 AMR AF: 0.00184

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000777

Gnomad4 OTH AF: 0.000705

Alfa AF: 0.000781 Hom.: 4

Bravo AF: 0.00229

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	4.8
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs138335499; hg19: chrX-12516835;