chr5-79396864-C-T

Position:

• chr5-79396864-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_004272.5(HOMER1):​c.835G>A​(p.Glu279Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HOMER1 NM_004272.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.39

Genes affected

HOMER1 (HGNC:17512): (homer scaffold protein 1) This gene encodes a member of the homer family of dendritic proteins. Members of this family regulate group 1 metabotrophic glutamate receptor function. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, HOMER1
• BP4: Computational evidence support a benign effect (MetaRNN=0.19696724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOMER1	NM_004272.5	c.835G>A	p.Glu279Lys	missense_variant	8/9	ENST00000334082.11
HOMER1	NM_001277077.1	c.445G>A	p.Glu149Lys	missense_variant	5/6
HOMER1	XM_047417894.1	c.643G>A	p.Glu215Lys	missense_variant	8/9
HOMER1	NM_001277078.1	c.528-20667G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOMER1	ENST00000334082.11	c.835G>A	p.Glu279Lys	missense_variant	8/9	1	NM_004272.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1452412 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 723022

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.835G>A (p.E279K) alteration is located in exon 8 (coding exon 8) of the HOMER1 gene. This alteration results from a G to A substitution at nucleotide position 835, causing the glutamic acid (E) at amino acid position 279 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.;T
Eigen	Benign	-0.026
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.2	M;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.014	D;D;D
Sift4G	Benign	0.25	T;T;D
Polyphen		0.017	B;B;B
Vest4		0.27
MutPred		0.28		Gain of MoRF binding (P = 0.0067);.;.;
MVP		0.64
MPC		1.2
ClinPred		0.89	D
GERP RS		5.8
Varity_R		0.30
gMVP		0.37

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: chr5-78692687;