rs1206233157

Variant names:

• chr19-18929578-G-C
• NM_004838.4:c.951C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-18929578-G-C
• chr19-18929578-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004838.4(HOMER3):​c.951C>G​(p.Ser317Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,393,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HOMER3 NM_004838.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.072393894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOMER3	NM_004838.4	c.951C>G	p.Ser317Arg	missense_variant	Exon 10 of 10	ENST00000392351.8	NP_004829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOMER3	ENST00000392351.8	c.951C>G	p.Ser317Arg	missense_variant	Exon 10 of 10	1	NM_004838.4	ENSP00000376162.2
ENSG00000268193	ENST00000596918.5	n.*167+1747C>G		intron_variant	Intron 4 of 6	5		ENSP00000469669.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1393584 Hom.: 0 Cov.: 43 AF XY: 0.00 AC XY: 0 AN XY: 687046

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: 0.00000186

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.044	.;.;T;T;.;.;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.71	T;.;.;.;T;T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.072	T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.29	.;.;N;N;.;.;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.62	N;.;N;N;.;.;N
REVEL	Benign	0.035
Sift	Benign	0.78	T;.;T;T;.;.;T
Sift4G	Benign	0.78	T;T;T;T;T;T;T
Polyphen		0.49	P;P;B;B;.;.;B
Vest4		0.097
MutPred		0.18		.;.;Loss of phosphorylation at S317 (P = 0.0024);Loss of phosphorylation at S317 (P = 0.0024);.;.;Loss of phosphorylation at S317 (P = 0.0024);
MVP		0.16
MPC		0.51
ClinPred		0.11	T
GERP RS		1.9
Varity_R		0.11
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-19040387;