3-129315485-T-G

Variant names:

• chr3-129315485-T-G
• rs2107706331
• NM_006026.4:c.418A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006026.4(H1-10):​c.418A>C​(p.Thr140Pro) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: H1-10 NM_006026.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.04
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054463595).

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.418A>C	p.Thr140Pro	missense	Exon 1 of 1	NP_006017.1	Q92522

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H1-10	ENST00000333762.6	TSL:6 MANE Select	c.418A>C	p.Thr140Pro	missense	Exon 1 of 1	ENSP00000329662.4	Q92522
	H1-10	ENST00000704995.1		c.571A>C	p.Thr191Pro	missense	Exon 1 of 1	ENSP00000516065.1	A0A994J4R3
	H1-10-AS1	ENST00000511998.1	TSL:5	n.94T>G		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	0.064
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.2
DANN	Benign	0.68
DEOGEN2	Benign	0.076	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.029
Sift	Benign	0.11	T
Sift4G	Benign	0.14	T
Polyphen		0.0040	B
Vest4		0.069
MutPred		0.20		Loss of phosphorylation at T140 (P = 0.0059)
MVP		0.072
MPC		0.85
ClinPred		0.064	T
GERP RS		-5.1
Varity_R		0.20
gMVP		0.27
Mutation Taster		=99/1	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

dbSNP: rs2107706331; hg19: chr3-129034328;