chr6-27838335-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM1

The NM_003510.3(H2AC15):c.5C>T(p.Ser2Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000628 in 1,575,628 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

H2AC15
NM_003510.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.12

Publications

2 publications found

Variant links:

Genes affected

H2AC15 (HGNC:4726): (H2A clustered histone 15) 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 H2A family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the small histone gene cluster on chromosome 6p22-p21.3. [provided by RefSeq, Aug 2015]

H2AC15 links:

H2BC15 (HGNC:4749): (H2B clustered histone 15) 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 H2B family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the small histone gene cluster on chromosome 6p22-p21.3. [provided by RefSeq, Aug 2015]

H2BC15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM1

In a modified_residue N-acetylserine (size 0) in uniprot entity H2A1_HUMAN

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
H2AC15	NM_003510.3 link	c.5C>T	p.Ser2Leu	missense_variant	Exon 1 of 1	ENST00000618958.2	NP_003501.1	P0C0S8A4FTV9
H2BC15	NM_003520.4 link	c.-327G>A		upstream_gene_variant		ENST00000612898.2	NP_003511.1	Q99877A0A024RCJ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
H2AC15	ENST00000618958.2 link	c.5C>T	p.Ser2Leu	missense_variant	Exon 1 of 1	6	NM_003510.3	ENSP00000482431.2	P0C0S8
H2AC15	ENST00000718365.1 link	c.5C>T	p.Ser2Leu	missense_variant	Exon 1 of 1			ENSP00000520791.1
H2BC15	ENST00000612898.2 link	c.-327G>A		upstream_gene_variant		6	NM_003520.4	ENSP00000483903.1	Q99877
H2BC15	ENST00000449538.3 link	n.-327G>A		upstream_gene_variant		1		ENSP00000446031.1	Q99877

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000727

AC:

AN:

220010

AF XY:

0.0000842

show subpopulations

Gnomad AFR exome

AF:

0.000255

Gnomad AMR exome

AF:

0.000140

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000115

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000591

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000611

AC:

AN:

1423522

Hom.:

Cov.:

AF XY:

0.0000624

AC XY:

AN XY:

704750

show subpopulations

African (AFR)

AF:

0.0000621

AC:

AN:

32182

American (AMR)

AF:

0.000130

AC:

AN:

38552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23348

East Asian (EAS)

AF:

0.00

AC:

AN:

39322

South Asian (SAS)

AF:

0.0000369

AC:

AN:

81250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51990

Middle Eastern (MID)

AF:

0.000903

AC:

AN:

5540

European-Non Finnish (NFE)

AF:

0.0000622

AC:

AN:

1092734

Other (OTH)

AF:

0.0000683

AC:

AN:

58604

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41478

American (AMR)

AF:

0.00

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000901

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000742

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 04, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.5C>T (p.S2L) alteration is located in exon 1 (coding exon 1) of the HIST1H2AK gene. This alteration results from a C to T substitution at nucleotide position 5, causing the serine (S) at amino acid position 2 to be replaced by a leucine (L). 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

0.038

BayesDel_noAF

Uncertain

0.11

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.82

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.60

MetaSVM

Uncertain

0.33

PhyloP100

4.1

PrimateAI

Pathogenic

0.83

Sift4G

Uncertain

0.023

Vest4

0.69

MVP

0.26

ClinPred

0.92

GERP RS

4.5

PromoterAI

-0.025

Neutral

(source)

gMVP

0.21

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr6-27838335-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over