2-96608899-C-G

Position:

• chr2-96608899-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001115016.3(KANSL3):​c.1549G>C​(p.Ala517Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 4.28

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36139143).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANSL3	NM_001115016.3	c.1549G>C	p.Ala517Pro	missense_variant	13/21	ENST00000431828.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANSL3	ENST00000431828.6	c.1549G>C	p.Ala517Pro	missense_variant	13/21	1	NM_001115016.3	P3

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The c.1549G>C (p.A517P) alteration is located in exon 13 (coding exon 12) of the KANSL3 gene. This alteration results from a G to C substitution at nucleotide position 1549, causing the alanine (A) at amino acid position 517 to be replaced by a proline (P). 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	0.17
BayesDel_addAF	Benign	-0.0085	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.15
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.48
MVP		0.15
MPC		0.60
ClinPred		0.77	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.54

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: chr2-97274636;