Variant 6-27865699-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003511.3(H2AC16):c.345G>T(p.Val115Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00727 in 1,614,236 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 60 hom. )

Consequence

H2AC16
NM_003511.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.858

Variant links:

Genes affected

H2AC16 (HGNC:4730): (H2A clustered histone 16) 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]

H2AC16 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 6-27865699-G-T is Benign according to our data. Variant chr6-27865699-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656317.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.858 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
H2AC16	NM_003511.3 linkuse as main transcript	c.345G>T	p.Val115Val	synonymous_variant	1/1	ENST00000613174.2	NP_003502.1	P0C0S8A4FTV9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H2AC16	ENST00000613174.2 linkuse as main transcript	c.345G>T	p.Val115Val	synonymous_variant	1/1	6	NM_003511.3	ENSP00000482538.2		P0C0S8

Frequencies

GnomAD3 genomes

AF:

0.00520

AC:

792

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00745

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00534

AC:

1344

AN:

251474

Hom.:

AF XY:

0.00554

AC XY:

753

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00341

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.000947

Gnomad FIN exome

AF:

0.0111

Gnomad NFE exome

AF:

0.00748

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.00749

AC:

10943

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00736

AC XY:

5352

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00387

Gnomad4 ASJ exome

AF:

0.00394

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00104

Gnomad4 FIN exome

AF:

0.0120

Gnomad4 NFE exome

AF:

0.00852

Gnomad4 OTH exome

AF:

0.00682

GnomAD4 genome

AF:

0.00520

AC:

792

AN:

152342

Hom.:

Cov.:

AF XY:

0.00510

AC XY:

380

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.0120

Gnomad4 NFE

AF:

0.00745

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00694

Hom.:

Bravo

AF:

0.00451

EpiCase

AF:

0.00714

EpiControl

AF:

0.00729

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

H2AC16: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

3.4

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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