Genetic Variant NM_001388459.1:c.290C>A (chrX-107533543-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.59

Publications

0 publications found

Variant links:

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 links:

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

FRMPD3-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25659898).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388459.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FRMPD3	NM_001388459.1	MANE Select	c.290C>A	p.Thr97Asn	missense	Exon 4 of 15	NP_001375388.1	Q5JV73
FRMPD3	NM_032428.2		c.389C>A	p.Thr130Asn	missense	Exon 5 of 16	NP_115804.1
FRMPD3	NM_001388462.1		c.-109+3032C>A		intron	N/A	NP_001375391.1	A0A804HJA6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FRMPD3	ENST00000683843.1	MANE Select	c.290C>A	p.Thr97Asn	missense	Exon 4 of 15	ENSP00000507942.1	Q5JV73
FRMPD3	ENST00000276185.9	TSL:5	c.290C>A	p.Thr97Asn	missense	Exon 5 of 16	ENSP00000276185.5	Q5JV73
FRMPD3	ENST00000439554.1	TSL:5	c.233C>A	p.Thr78Asn	missense	Exon 3 of 14	ENSP00000398668.1	A0A0A0MSP7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000366

AC:

AN:

1092494

Hom.:

Cov.:

AF XY:

0.00000836

AC XY:

AN XY:

358716

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26295

American (AMR)

AF:

0.00

AC:

AN:

34958

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19339

East Asian (EAS)

AF:

0.00

AC:

AN:

30117

South Asian (SAS)

AF:

0.00

AC:

AN:

53491

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39435

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4120

European-Non Finnish (NFE)

AF:

0.00000477

AC:

AN:

838806

Other (OTH)

AF:

0.00

AC:

AN:

45933

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.014

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.78

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.1

PhyloP100

4.6

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.048

Sift

Benign

0.23

Sift4G

Benign

0.090

Vest4

0.73

MutPred

0.41

Gain of relative solvent accessibility (P = 0.0479)

MVP

0.51

MPC

0.16

ClinPred

0.67

GERP RS

4.6

Varity_R

0.42

gMVP

0.34

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over