12-48329761-GC-CG

Variant names:

• chr12-48329761-GC-CG
• NM_181788.1:c.470_471delGCinsCG
• H1-7 p.Arg157Pro

Variant summary

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

The NM_181788.1(H1-7):​c.470_471delGCinsCG​(p.Arg157Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R157H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: H1-7 NM_181788.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362
• 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.

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.470_471delGCinsCG	p.Arg157Pro	missense	N/A	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.470_471delGCinsCG	p.Arg157Pro	missense	N/A	ENSP00000334805.1	Q75WM6
	ENSG00000293682	ENST00000717861.1		n.312-27692_312-27691delGCinsCG		intron	N/A
	ENSG00000257735	ENST00000717862.1		n.400+14439_400+14440delGCinsCG		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-48723544;