Variant 6-26271339-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003534.3(H3C8):c.46G>A(p.Ala16Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,324 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

H3C8
NM_003534.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.03

Variant links:

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]

H3C8 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

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=0.23677221).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
H3C8	NM_003534.3 linkuse as main transcript	c.46G>A	p.Ala16Thr	missense_variant	1/1	ENST00000614378.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Appris
H3C8	ENST00000614378.2 linkuse as main transcript	c.46G>A	p.Ala16Thr	missense_variant	1/1	NM_003534.3	P1
	ENST00000707189.1 linkuse as main transcript	n.999+147168C>T		intron_variant, non_coding_transcript_variant
	ENST00000707191.1 linkuse as main transcript	n.1000+113218C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248722

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461324

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727050

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

May 30, 2023

The c.46G>A (p.A16T) alteration is located in exon 1 (coding exon 1) of the HIST1H3G gene. This alteration results from a G to A substitution at nucleotide position 46, causing the alanine (A) at amino acid position 16 to be replaced by a threonine (T). 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

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Benign

0.85

Eigen

Benign

0.11

Eigen_PC

Benign

0.086

FATHMM_MKL

Uncertain

0.88

M_CAP

Benign

0.012

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.77

MutationTaster

Benign

0.88

PrimateAI

Uncertain

0.74

Sift4G

Benign

0.14

Vest4

0.30

MVP

0.10

ClinPred

0.98

GERP RS

3.7

gMVP

0.30

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over