chr2-96604334-C-A

Variant names:

• chr2-96604334-C-A
• NM_001115016.3:c.2065G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001115016.3(KANSL3):​c.2065G>T​(p.Val689Leu) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KANSL3 NM_001115016.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.365
• Publications: 0 publications found

Genes affected

KANSL3 (HGNC:25473): (KAT8 regulatory NSL complex subunit 3) Involved in histone H4-K16 acetylation; histone H4-K5 acetylation; and histone H4-K8 acetylation. Located in nucleoplasm. Part of histone acetyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051947355).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001115016.3. 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
	KANSL3	NM_001115016.3	MANE Select	c.2065G>T	p.Val689Leu	missense	Exon 17 of 21	NP_001108488.1	Q9P2N6-3
	KANSL3	NM_001349256.2		c.2143G>T	p.Val715Leu	missense	Exon 18 of 22	NP_001336185.1
	KANSL3	NM_001349257.2		c.2143G>T	p.Val715Leu	missense	Exon 18 of 22	NP_001336186.1	Q9P2N6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANSL3	ENST00000431828.6	TSL:1 MANE Select	c.2065G>T	p.Val689Leu	missense	Exon 17 of 21	ENSP00000396749.1	Q9P2N6-3
	KANSL3	ENST00000354204.10	TSL:1	n.*1907G>T		non_coding_transcript_exon	Exon 17 of 21	ENSP00000346144.7	F8WEN2
	KANSL3	ENST00000420155.5	TSL:1	n.2143G>T		non_coding_transcript_exon	Exon 18 of 21	ENSP00000414426.1	Q9P2N6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Benign	0.084
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.88
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.36
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.057
Sift	Benign	0.36	T
Sift4G	Benign	0.62	T
Polyphen		0.0	B
Vest4		0.091
MVP		0.18
MPC		0.20
ClinPred		0.055	T
GERP RS		3.6
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
gMVP		0.17
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

hg19: chr2-97270071;