12-48329452-C-T

Variant names:

• chr12-48329452-C-T
• NM_181788.1:c.161C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181788.1(H1-7):​c.161C>T​(p.Ser54Leu) 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. 14/21 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: -0.225

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06974873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
H1-7	NM_181788.1	c.161C>T	p.Ser54Leu	missense_variant	Exon 1 of 1	ENST00000335017.1	NP_861453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H1-7	ENST00000335017.1	c.161C>T	p.Ser54Leu	missense_variant	Exon 1 of 1	6	NM_181788.1	ENSP00000334805.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.161C>T (p.S54L) alteration is located in exon 1 (coding exon 1) of the H1FNT gene. This alteration results from a C to T substitution at nucleotide position 161, causing the serine (S) at amino acid position 54 to be replaced by a leucine (L). 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	0.14
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.79
DEOGEN2	Benign	0.35	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.010
Sift	Benign	0.20	T
Sift4G	Benign	0.26	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.23		Loss of loop (P = 0.0203);
MVP		0.099
MPC		0.16
ClinPred		0.024	T
GERP RS		-2.2
Varity_R		0.042
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-48723235;