NM_001388459.1:c.290C>A

Variant names:

• chrX-107533543-C-A
• NM_001388459.1:c.290C>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001388459.1(FRMPD3):​c.290C>A​(p.Thr97Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000366 in 1,092,494 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T97S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000037 (0 hom. 3 hem.)
• Consequence: FRMPD3 NM_001388459.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.59

Genes affected

FRMPD3 (HGNC:29382): (FERM and PDZ domain containing 3) This gene encodes a protein that contains a PDZ (post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1) domain at the N-terminus followed by a FERM domain. The encoded protein is involved in signal transduction. The PDZ domain is thought to function in protein-protein interactions, mainly by binding to specific C-terminal peptides of other proteins. The FERM domain is found in proteins that are localized to the plasma membrane and are associated with the cytoskeleton. [provided by RefSeq, May 2017]

FRMPD3-AS1 (HGNC:41239): (FRMPD3 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25659898).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD3	NM_001388459.1	c.290C>A	p.Thr97Asn	missense_variant	Exon 4 of 15	ENST00000683843.1	NP_001375388.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD3	ENST00000683843.1	c.290C>A	p.Thr97Asn	missense_variant	Exon 4 of 15		NM_001388459.1	ENSP00000507942.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000366 AC: 4 AN: 1092494 Hom.: 0 Cov.: 28 AF XY: 0.00000836 AC XY: 3 AN XY: 358716

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000477

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T;T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T;T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.1	L;.
PROVEAN	Uncertain	-2.5	N;N
REVEL	Benign	0.048
Sift	Benign	0.23	T;T
Sift4G	Benign	0.090	T;T
Vest4		0.73
MutPred		0.41		Gain of relative solvent accessibility (P = 0.0479);.;
MVP		0.51
MPC		0.16
ClinPred		0.67	D
GERP RS		4.6
Varity_R		0.42
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-106776773;