chr5-79376070-C-A

Position:

• chr5-79376070-C-A

Variant summary

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

The NM_004272.5(HOMER1):​c.1004G>T​(p.Gly335Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,218 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HOMER1 NM_004272.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.53

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOMER1	NM_004272.5	c.1004G>T	p.Gly335Val	missense_variant	9/9	ENST00000334082.11	NP_004263.1
HOMER1	NM_001277077.1	c.614G>T	p.Gly205Val	missense_variant	6/6		NP_001264006.1
HOMER1	XM_047417894.1	c.812G>T	p.Gly271Val	missense_variant	9/9		XP_047273850.1
HOMER1	NM_001277078.1	c.*121G>T		3_prime_UTR_variant	6/6		NP_001264007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOMER1	ENST00000334082.11	c.1004G>T	p.Gly335Val	missense_variant	9/9	1	NM_004272.5	ENSP00000334382	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461218 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726908

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Sep 17, 2021

The c.1004G>T (p.G335V) alteration is located in exon 9 (coding exon 9) of the HOMER1 gene. This alteration results from a G to T substitution at nucleotide position 1004, causing the glycine (G) at amino acid position 335 to be replaced by a valine (V). 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	0.29
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;.;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.4	L;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Uncertain	0.35
Sift	Benign	0.69	T;T;T
Sift4G	Benign	0.53	T;T;T
Polyphen		0.97	D;D;P
Vest4		0.53
MutPred		0.37		Gain of methylation at K336 (P = 0.0374);.;.;
MVP		0.60
MPC		2.2
ClinPred		0.89	D
GERP RS		5.7
Varity_R		0.39
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr5-78671893;