dbSNP rs1208716516: H1-10:p.Ala141Ser (chr3-129315482-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006026.4(H1-10):c.421G>T(p.Ala141Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000741 in 1,349,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A141T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

H1-10
NM_006026.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.569

Publications

0 publications found

Variant links:

Genes affected

H1-10 (HGNC:4722): (H1.10 linker histone) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene encodes a replication-independent histone that is a member of the histone H1 family. [provided by RefSeq, Oct 2015]

H1-10 links:

H1-10-AS1 (HGNC:27953): (H1-10 antisense RNA 1)

H1-10-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0910978).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006026.4. 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
	H1-10	NM_006026.4	MANE Select	c.421G>T	p.Ala141Ser	missense	Exon 1 of 1	NP_006017.1	Q92522

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
H1-10	ENST00000333762.6	TSL:6 MANE Select	c.421G>T	p.Ala141Ser	missense	Exon 1 of 1	ENSP00000329662.4	Q92522
H1-10	ENST00000704995.1		c.574G>T	p.Ala192Ser	missense	Exon 1 of 1	ENSP00000516065.1	A0A994J4R3
H1-10-AS1	ENST00000511998.1	TSL:5	n.91C>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.41e-7

AC:

AN:

1349778

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

666132

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

28918

American (AMR)

AF:

0.00

AC:

AN:

29344

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23470

East Asian (EAS)

AF:

0.00

AC:

AN:

33542

South Asian (SAS)

AF:

0.00

AC:

AN:

75040

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35776

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4292

European-Non Finnish (NFE)

AF:

9.41e-7

AC:

AN:

1063258

Other (OTH)

AF:

0.00

AC:

AN:

56138

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.11

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.45

M_CAP

Benign

0.022

MetaRNN

Benign

0.091

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

PhyloP100

0.57

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.22

REVEL

Benign

0.014

Sift

Benign

0.26

Sift4G

Benign

0.22

Polyphen

0.0060

Vest4

0.063

MutPred

0.20

Gain of glycosylation at A141 (P = 8e-04)

MVP

0.16

MPC

0.55

ClinPred

0.096

GERP RS

-2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.19

Mutation Taster

=100/0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over