NM_003547.3:c.151A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003547.3(H4C7):​c.151A>G​(p.Ile51Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000818 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000085 ( 0 hom. )

Consequence

H4C7
NM_003547.3 missense

Scores

4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.36
Variant links:
Genes affected
H4C7 (HGNC:4792): (H4 clustered histone 7) 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 H4 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
H4C7NM_003547.3 linkc.151A>G p.Ile51Val missense_variant Exon 1 of 1 ENST00000611444.2 NP_003538.1 Q99525

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
H4C7ENST00000611444.2 linkc.151A>G p.Ile51Val missense_variant Exon 1 of 1 6 NM_003547.3 ENSP00000477870.2 Q99525
ENSG00000291336ENST00000707189.1 linkn.999+122656T>C intron_variant Intron 1 of 1
ENSG00000291338ENST00000707191.1 linkn.1000+88706T>C intron_variant Intron 1 of 1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152146
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000115
AC:
29
AN:
251394
Hom.:
0
AF XY:
0.000118
AC XY:
16
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000158
Gnomad OTH exome
AF:
0.000978
GnomAD4 exome
AF:
0.0000848
AC:
124
AN:
1461888
Hom.:
0
Cov.:
31
AF XY:
0.0000921
AC XY:
67
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.0000755
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152264
Hom.:
0
Cov.:
32
AF XY:
0.0000940
AC XY:
7
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000270
Hom.:
0
Bravo
AF:
0.0000756
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000988
AC:
12
EpiCase
AF:
0.000218
EpiControl
AF:
0.000296

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.151A>G (p.I51V) alteration is located in exon 1 (coding exon 1) of the HIST1H4G gene. This alteration results from a A to G substitution at nucleotide position 151, causing the isoleucine (I) at amino acid position 51 to be replaced by a valine (V). 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
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
22
DANN
Benign
0.65
DEOGEN2
Benign
0.041
T
Eigen
Benign
0.061
Eigen_PC
Benign
0.022
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.0056
T
MetaRNN
Uncertain
0.61
D
MetaSVM
Benign
-0.79
T
PrimateAI
Uncertain
0.78
T
Sift4G
Benign
0.20
T
Polyphen
0.55
P
Vest4
0.69
MVP
0.33
ClinPred
0.55
D
GERP RS
3.2
Varity_R
0.038
gMVP
0.71

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.

Other links and lift over

dbSNP: rs370289402; hg19: chr6-26247055; API