19-18931578-A-C

Variant names:

• chr19-18931578-A-C
• NM_004838.4:c.738T>G
• HOMER3 p.Gly246Gly

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004838.4(HOMER3):​c.738T>G​(p.Gly246Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G246G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HOMER3 NM_004838.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.01
• Publications: 0 publications found

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]

ENSG00000268193 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP7: Synonymous conserved (PhyloP=-6.01 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOMER3	NM_004838.4	MANE Select	c.738T>G	p.Gly246Gly	synonymous	Exon 8 of 10	NP_004829.3
	HOMER3	NM_001145722.2		c.738T>G	p.Gly246Gly	synonymous	Exon 8 of 10	NP_001139194.1	Q9NSC5-1
	HOMER3	NM_001145721.1		c.738T>G	p.Gly246Gly	synonymous	Exon 8 of 10	NP_001139193.1	Q9NSC5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOMER3	ENST00000392351.8	TSL:1 MANE Select	c.738T>G	p.Gly246Gly	synonymous	Exon 8 of 10	ENSP00000376162.2	Q9NSC5-1
	HOMER3	ENST00000539827.5	TSL:1	c.738T>G	p.Gly246Gly	synonymous	Exon 7 of 9	ENSP00000439937.1	Q9NSC5-1
	HOMER3	ENST00000542541.6	TSL:1	c.738T>G	p.Gly246Gly	synonymous	Exon 8 of 10	ENSP00000446026.1	Q9NSC5-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.12
DANN	Benign	0.69
PhyloP100		-6.0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-19042387;