3-136151671-A-ATTACT

Variant names:

• chr3-136151671-A-ATTACT
• NM_018133.4:c.1209_1210insAGTAA

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_018133.4(MSL2):​c.1209_1210insAGTAA​(p.Thr405AsnfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MSL2 NM_018133.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.701

Genes affected

MSL2 (HGNC:25544): (MSL complex subunit 2) Predicted to enable ubiquitin protein ligase activity. Involved in histone H4-K16 acetylation. Part of MSL complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.303 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-136151671-A-ATTACT is Pathogenic according to our data. Variant chr3-136151671-A-ATTACT is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3773655.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSL2	NM_018133.4	c.1209_1210insAGTAA	p.Thr405AsnfsTer6	frameshift_variant	Exon 2 of 2	ENST00000309993.3	NP_060603.2
MSL2	NM_001145417.2	c.987_988insAGTAA	p.Thr331AsnfsTer6	frameshift_variant	Exon 2 of 2		NP_001138889.1
MSL2	XM_005247571.4	c.987_988insAGTAA	p.Thr331AsnfsTer6	frameshift_variant	Exon 2 of 2		XP_005247628.1
MSL2	XM_011512949.3	c.987_988insAGTAA	p.Thr331AsnfsTer6	frameshift_variant	Exon 2 of 2		XP_011511251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSL2	ENST00000309993.3	c.1209_1210insAGTAA	p.Thr405AsnfsTer6	frameshift_variant	Exon 2 of 2	1	NM_018133.4	ENSP00000311827.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Karayol-Borroto-Haghshenas neurodevelopmental syndrome Pathogenic:1

Mar 04, 2025

Institute of Human Genetics, University of Leipzig Medical Center

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Criteria applied: PVS1_STR,PM2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr3-135870513;