6-26271278-A-C

Variant names:

• chr6-26271278-A-C
• rs2113607390
• NM_003534.3:c.107T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003534.3(H3C8):​c.107T>G​(p.Val36Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: H3C8 NM_003534.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.26
• Publications: 0 publications found

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]

ENSG00000291336 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003534.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H3C8	NM_003534.3	MANE Select	c.107T>G	p.Val36Gly	missense	Exon 1 of 1	NP_003525.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H3C8	ENST00000614378.2	TSL:6 MANE Select	c.107T>G	p.Val36Gly	missense	Exon 1 of 1	ENSP00000484638.1	P68431
	ENSG00000291336	ENST00000707189.1		n.999+147107A>C		intron	N/A
	ENSG00000291338	ENST00000707191.1		n.1000+113157A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	27
DANN	Benign	0.95
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.82	D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.82	T
PhyloP100		7.3
PrimateAI	Uncertain	0.70	T
Sift4G	Uncertain	0.031	D
Vest4		0.58
MVP		0.36
ClinPred		0.97	D
GERP RS		4.6
PromoterAI		0.0016	Neutral
gMVP		0.41
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs2113607390; hg19: chr6-26271506;