Variant 19-18931578-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004838.4(HOMER3):c.738T>C(p.Gly246Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 1,612,976 control chromosomes in the GnomAD database, including 345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 172 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 173 hom. )

Consequence

HOMER3
NM_004838.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -6.01

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 19-18931578-A-G is Benign according to our data. Variant chr19-18931578-A-G is described in ClinVar as [Benign]. Clinvar id is 781464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOMER3	NM_004838.4 linkuse as main transcript	c.738T>C	p.Gly246Gly	synonymous_variant	8/10	ENST00000392351.8	NP_004829.3	Q9NSC5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HOMER3	ENST00000392351.8 linkuse as main transcript	c.738T>C	p.Gly246Gly	synonymous_variant	8/10	1	NM_004838.4	ENSP00000376162.2	Q9NSC5-1
ENSG00000268193	ENST00000596918.5 linkuse as main transcript	n.*11T>C		non_coding_transcript_exon_variant	3/7	5		ENSP00000469669.1	M0R1B8
ENSG00000268193	ENST00000596918.5 linkuse as main transcript	n.*11T>C		3_prime_UTR_variant	3/7	5		ENSP00000469669.1	M0R1B8

Frequencies

GnomAD3 genomes

AF:

0.0253

AC:

3848

AN:

152028

Hom.:

171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0868

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000324

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.00657

AC:

1645

AN:

250268

Hom.:

AF XY:

0.00483

AC XY:

654

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.0879

Gnomad AMR exome

AF:

0.00350

Gnomad ASJ exome

AF:

0.00469

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000283

Gnomad OTH exome

AF:

0.00425

GnomAD4 exome

AF:

0.00272

AC:

3980

AN:

1460830

Hom.:

173

Cov.:

AF XY:

0.00236

AC XY:

1714

AN XY:

726708

show subpopulations

Gnomad4 AFR exome

AF:

0.0920

Gnomad4 AMR exome

AF:

0.00474

Gnomad4 ASJ exome

AF:

0.00436

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000123

Gnomad4 OTH exome

AF:

0.00653

GnomAD4 genome

AF:

0.0254

AC:

3871

AN:

152146

Hom.:

172

Cov.:

AF XY:

0.0245

AC XY:

1819

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0871

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000324

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.0294

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.13

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over