chr22-37806022-C-T

Variant names:

• chr22-37806022-C-T
• NM_005318.4:c.478C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005318.4(H1-0):​c.478C>T​(p.Pro160Ser) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: H1-0 NM_005318.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.24
• Publications: 0 publications found

Genes affected

H1-0 (HGNC:4714): (H1.0 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 is intronless and encodes a replication-independent histone that is a member of the histone H1 family. [provided by RefSeq, Oct 2015]

ACMG classification

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=0.17454633).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005318.4. 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
	H1-0	NM_005318.4	MANE Select	c.478C>T	p.Pro160Ser	missense	Exon 1 of 1	NP_005309.1	P07305-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H1-0	ENST00000340857.4	TSL:6 MANE Select	c.478C>T	p.Pro160Ser	missense	Exon 1 of 1	ENSP00000344504.2	P07305-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Uncertain	24
DANN	Benign	0.88
DEOGEN2	Uncertain	0.60	D
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.024
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.2
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.025
Sift	Benign	0.17	T
Sift4G	Uncertain	0.038	D
Polyphen		0.13	B
Vest4		0.16
MutPred		0.27		Gain of phosphorylation at P160 (P = 0.0041)
MVP		0.49
MPC		0.55
ClinPred		0.23	T
GERP RS		4.3
Varity_R		0.15
gMVP		0.044
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

hg19: chr22-38202029;