NM_005320.3:c.554_556delAAG

Variant names:

• chr6-26234377-GCTT-G
• rs199868143
• NM_005320.3:c.554_556delAAG

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PM4_Supporting BP6_Moderate BS2

The NM_005320.3(H1-3):​c.554_556delAAG​(p.Lys185_Ala186delinsThr) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00602 in 1,614,242 control chromosomes in the GnomAD database, including 42 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0073 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (37 hom.)
• Consequence: H1-3 NM_005320.3 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.55
• Publications: 1 publications found

Genes affected

H1-3 (HGNC:4717): (H1.3 linker histone, cluster member) Histones are basic nuclear proteins responsible for nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H1 family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6. [provided by RefSeq, Aug 2015]

ENSG00000291336 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_005320.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 6-26234377-GCTT-G is Benign according to our data. Variant chr6-26234377-GCTT-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2656310.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005320.3. 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
	H1-3	NM_005320.3	MANE Select	c.554_556delAAG	p.Lys185_Ala186delinsThr	disruptive_inframe_deletion	Exon 1 of 1	NP_005311.1	P16402

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H1-3	ENST00000244534.7	TSL:6 MANE Select	c.554_556delAAG	p.Lys185_Ala186delinsThr	disruptive_inframe_deletion	Exon 1 of 1	ENSP00000244534.6	P16402
	ENSG00000291336	ENST00000707189.1		n.999+110207_999+110209delCTT		intron	N/A
	ENSG00000291338	ENST00000707191.1		n.1000+76257_1000+76259delCTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00727 AC: 1106 AN: 152236 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00888

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.00496

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00651

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00579 AC: 1455 AN: 251490 AF XY: 0.00575

Gnomad AFR exome AF: 0.00929

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.0132

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0144

Gnomad NFE exome AF: 0.00599

Gnomad OTH exome AF: 0.00505

GnomAD4 exome AF: 0.00589 AC: 8610 AN: 1461888 Hom.: 37 AF XY: 0.00596 AC XY: 4337 AN XY: 727242

African (AFR) AF: 0.00920 AC: 308 AN: 33480

American (AMR) AF: 0.00197 AC: 88 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0128 AC: 335 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00290 AC: 250 AN: 86258

European-Finnish (FIN) AF: 0.0149 AC: 795 AN: 53418

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5768

European-Non Finnish (NFE) AF: 0.00584 AC: 6495 AN: 1112012

Other (OTH) AF: 0.00533 AC: 322 AN: 60392

GnomAD4 genome AF: 0.00728 AC: 1109 AN: 152354 Hom.: 5 Cov.: 32 AF XY: 0.00753 AC XY: 561 AN XY: 74504

African (AFR) AF: 0.00887 AC: 369 AN: 41584

American (AMR) AF: 0.00438 AC: 67 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5186

South Asian (SAS) AF: 0.00538 AC: 26 AN: 4830

European-Finnish (FIN) AF: 0.0132 AC: 140 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00653 AC: 444 AN: 68030

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00840 Hom.: 2

Bravo AF: 0.00635

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00578

EpiControl AF: 0.00693

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.6
Mutation Taster		=152/48	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: rs199868143; hg19: chr6-26234605;