Genetic Variant ENST00000542541.6:c.-365T>C (chr19-18940148-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000542541.6(HOMER3):c.-365T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,468 control chromosomes in the GnomAD database, including 10,553 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.35 ( 10513 hom., cov: 32)

Exomes 𝑓: 0.40 ( 40 hom. )

Consequence

HOMER3
ENST00000542541.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0730

Publications

15 publications found

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:

HOMER3-AS1 (HGNC:53775): (HOMER3 antisense RNA 1)

HOMER3-AS1 links:

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new If you want to explore the variant's impact on the transcript ENST00000542541.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000542541.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HOMER3	NM_004838.4	MANE Select	c.-68+903T>C	intron	N/A	NP_004829.3
HOMER3	NM_001145722.2		c.-365T>C	5_prime_UTR	Exon 1 of 10	NP_001139194.1	Q9NSC5-1
HOMER3	NM_001145721.1		c.-68+173T>C	intron	N/A	NP_001139193.1	Q9NSC5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HOMER3	ENST00000542541.6	TSL:1	c.-365T>C	5_prime_UTR	Exon 1 of 10	ENSP00000446026.1	Q9NSC5-1
HOMER3	ENST00000392351.8	TSL:1 MANE Select	c.-68+903T>C	intron	N/A	ENSP00000376162.2	Q9NSC5-1
HOMER3	ENST00000971945.1		c.-278T>C	5_prime_UTR	Exon 1 of 10	ENSP00000642004.1

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

53096

AN:

151960

Hom.:

10521

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.483

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.400

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.531

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.441

Gnomad OTH

AF:

0.332

GnomAD4 exome

AF:

0.403

AC:

157

AN:

390

Hom.:

Cov.:

AF XY:

0.351

AC XY:

AN XY:

268

show subpopulations

African (AFR)

AF:

0.700

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.417

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.395

AC:

136

AN:

344

Other (OTH)

AF:

0.429

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.349

AC:

53084

AN:

152078

Hom.:

10513

Cov.:

AF XY:

0.350

AC XY:

26026

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.169

AC:

7035

AN:

41530

American (AMR)

AF:

0.298

AC:

4553

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1200

AN:

3468

East Asian (EAS)

AF:

0.400

AC:

2060

AN:

5150

South Asian (SAS)

AF:

0.295

AC:

1425

AN:

4824

European-Finnish (FIN)

AF:

0.531

AC:

5620

AN:

10592

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.441

AC:

29967

AN:

67930

Other (OTH)

AF:

0.327

AC:

690

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1675

3350

5024

6699

8374

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.407

Hom.:

17346

Bravo

AF:

0.326

Asia WGS

AF:

0.286

AC:

994

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

0.073

PromoterAI

-0.033

Neutral

(source)

Mutation Taster

=299/1

polymorphism (auto)

(source)

Splicing

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over