6-26271002-G-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_003534.3(H3C8):āc.383C>Gā(p.Ala128Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000179 in 1,614,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000072 ( 0 hom., cov: 32)
Exomes š: 0.00019 ( 0 hom. )
Consequence
H3C8
NM_003534.3 missense
NM_003534.3 missense
Scores
3
6
3
Clinical Significance
Conservation
PhyloP100: 6.77
Genes affected
H3C8 (HGNC:4772): (H3 clustered histone 8) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H3 family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6. [provided by RefSeq, Aug 2015]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.4202866).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
H3C8 | NM_003534.3 | c.383C>G | p.Ala128Gly | missense_variant | 1/1 | ENST00000614378.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
H3C8 | ENST00000614378.2 | c.383C>G | p.Ala128Gly | missense_variant | 1/1 | NM_003534.3 | P1 | ||
ENST00000707189.1 | n.999+146831G>C | intron_variant, non_coding_transcript_variant | |||||||
ENST00000707191.1 | n.1000+112881G>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152236Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
11
AN:
152236
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000835 AC: 21AN: 251464Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135906
GnomAD3 exomes
AF:
AC:
21
AN:
251464
Hom.:
AF XY:
AC XY:
13
AN XY:
135906
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000190 AC: 278AN: 1461890Hom.: 0 Cov.: 31 AF XY: 0.000162 AC XY: 118AN XY: 727246
GnomAD4 exome
AF:
AC:
278
AN:
1461890
Hom.:
Cov.:
31
AF XY:
AC XY:
118
AN XY:
727246
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74384
GnomAD4 genome
AF:
AC:
11
AN:
152236
Hom.:
Cov.:
32
AF XY:
AC XY:
6
AN XY:
74384
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
2
ExAC
AF:
AC:
15
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 29, 2023 | The c.383C>G (p.A128G) alteration is located in exon 1 (coding exon 1) of the HIST1H3G gene. This alteration results from a C to G substitution at nucleotide position 383, causing the alanine (A) at amino acid position 128 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
Sift4G
Pathogenic
D
Vest4
MVP
ClinPred
D
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at