rs913538882

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004838.4(HOMER3):c.683G>A(p.Arg228Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000203 in 1,529,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

HOMER3
NM_004838.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

Publications

0 publications found

Variant links:

Genes affected

HOMER3 (HGNC:17514): (homer scaffold protein 3) This gene encodes a member of the HOMER family of postsynaptic density scaffolding proteins that share a similar domain structure consisting of an N-terminal Enabled/vasodilator-stimulated phosphoprotein homology 1 domain which mediates protein-protein interactions, and a carboxy-terminal coiled-coil domain and two leucine zipper motifs that are involved in self-oligomerization. The encoded protein binds numerous other proteins including group I metabotropic glutamate receptors, inositol 1,4,5-trisphosphate receptors and amyloid precursor proteins and has been implicated in diverse biological functions such as neuronal signaling, T-cell activation and trafficking of amyloid beta peptides. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

HOMER3 links:

ENSG00000268193 (HGNC:):

ENSG00000268193 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1621697).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004838.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HOMER3	NM_004838.4	MANE Select	c.683G>A	p.Arg228Gln	missense	Exon 7 of 10	NP_004829.3
HOMER3	NM_001145722.2		c.683G>A	p.Arg228Gln	missense	Exon 7 of 10	NP_001139194.1	Q9NSC5-1
HOMER3	NM_001145721.1		c.683G>A	p.Arg228Gln	missense	Exon 7 of 10	NP_001139193.1	Q9NSC5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HOMER3	ENST00000392351.8	TSL:1 MANE Select	c.683G>A	p.Arg228Gln	missense	Exon 7 of 10	ENSP00000376162.2	Q9NSC5-1
HOMER3	ENST00000539827.5	TSL:1	c.683G>A	p.Arg228Gln	missense	Exon 6 of 9	ENSP00000439937.1	Q9NSC5-1
HOMER3	ENST00000542541.6	TSL:1	c.683G>A	p.Arg228Gln	missense	Exon 7 of 10	ENSP00000446026.1	Q9NSC5-1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000288

AC:

AN:

138820

AF XY:

0.0000402

show subpopulations

Gnomad AFR exome

AF:

0.000139

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:

0.0000192

Gnomad OTH exome

AF:

0.000501

GnomAD4 exome

AF:

0.0000145

AC:

AN:

1377210

Hom.:

Cov.:

AF XY:

0.0000192

AC XY:

AN XY:

677136

show subpopulations

African (AFR)

AF:

0.000355

AC:

AN:

30944

American (AMR)

AF:

0.000118

AC:

AN:

33774

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24538

East Asian (EAS)

AF:

0.00

AC:

AN:

35266

South Asian (SAS)

AF:

0.00

AC:

AN:

78010

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45070

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3996

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1068698

Other (OTH)

AF:

0.0000527

AC:

AN:

56914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

AF:

0.0000723

AC:

AN:

152048

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.0000967

AC:

AN:

41372

American (AMR)

AF:

0.000393

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000181

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

Eigen

Benign

0.17

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.84

M_CAP

Benign

0.033

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

2.4

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.14

Sift

Uncertain

0.027

Sift4G

Uncertain

0.021

Polyphen

0.83

Vest4

0.32

MutPred

0.16

Loss of MoRF binding (P = 0.0324)

MVP

0.26

MPC

0.52

ClinPred

0.091

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.43

gMVP

0.46

Mutation Taster

=64/36

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over