chr12-48329569-A-T

Variant names:

• chr12-48329569-A-T
• rs1280196944
• NM_181788.1:c.278A>T

Variant summary

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

The NM_181788.1(H1-7):​c.278A>T​(p.Lys93Met) 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. 13/22 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: H1-7 NM_181788.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.480
• Publications: 0 publications found

Genes affected

H1-7 (HGNC:24893): (H1.7 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. The related mouse gene encodes a testis specific protein that is required for spermatogenesis and male fertility. [provided by RefSeq, Oct 2015]

ENSG00000293682 (HGNC:):

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=0.19988096).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181788.1. 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
	H1-7	NM_181788.1	MANE Select	c.278A>T	p.Lys93Met	missense	Exon 1 of 1	NP_861453.1	Q75WM6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H1-7	ENST00000335017.1	TSL:6 MANE Select	c.278A>T	p.Lys93Met	missense	Exon 1 of 1	ENSP00000334805.1	Q75WM6
	ENSG00000293682	ENST00000717861.1		n.312-27884A>T		intron	N/A
	ENSG00000257735	ENST00000717862.1		n.400+14247A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

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	Uncertain	0.38
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Benign	0.058
Eigen_PC	Benign	-0.084
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.48
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.050
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.27		Loss of solvent accessibility (P = 0.0187)
MVP		0.49
MPC		0.82
ClinPred		0.98	D
GERP RS		2.3
Varity_R		0.17
gMVP		0.32
Mutation Taster		=97/3	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: rs1280196944; hg19: chr12-48723352;