NM_005321.3:c.53C>G

Variant names:

• chr6-26156443-C-G
• rs775335777
• NM_005321.3:c.53C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1 PM2 BP4_Strong

The NM_005321.3(H1-4):​c.53C>G​(p.Thr18Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: H1-4 NM_005321.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.05

Genes affected

H1-4 (HGNC:4718): (H1.4 linker histone, cluster member) Histones are basic nuclear proteins responsible for 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 H1 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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM1: In a modified_residue Phosphothreonine (size 0) in uniprot entity H14_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061849177).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
H1-4	NM_005321.3	c.53C>G	p.Thr18Ser	missense_variant	Exon 1 of 1	ENST00000304218.6	NP_005312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H1-4	ENST00000304218.6	c.53C>G	p.Thr18Ser	missense_variant	Exon 1 of 1	6	NM_005321.3	ENSP00000307705.4
ENSG00000291336	ENST00000707189.1	n.999+32272C>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Benign	0.50
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.065	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.29	N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.052
Sift	Benign	0.76	T
Sift4G	Benign	0.54	T
Polyphen		0.23	B
Vest4		0.32
MutPred		0.18		Gain of glycosylation at T18 (P = 0.0478);
MVP		0.048
ClinPred		0.19	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.092
gMVP		0.39

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

Other links and lift over

dbSNP: rs775335777; hg19: chr6-26156671;