chr2-96604334-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 14/19 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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANSL3	NM_001115016.3	c.2065G>T	p.Val689Leu	missense_variant	Exon 17 of 21	ENST00000431828.6	NP_001108488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANSL3	ENST00000431828.6	c.2065G>T	p.Val689Leu	missense_variant	Exon 17 of 21	1	NM_001115016.3	ENSP00000396749.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2065G>T (p.V689L) alteration is located in exon 17 (coding exon 16) of the KANSL3 gene. This alteration results from a G to T substitution at nucleotide position 2065, causing the valine (V) at amino acid position 689 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	0.084
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
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

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: chr2-97270071;