chr2-96605415-T-C

Variant names:

• chr2-96605415-T-C
• rs200065186
• NM_001115016.3:c.1838A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001115016.3(KANSL3):​c.1838A>G​(p.Lys613Arg) 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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K613T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KANSL3 NM_001115016.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.80
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.101524055).

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.1838A>G	p.Lys613Arg	missense	Exon 15 of 21	NP_001108488.1	Q9P2N6-3
	KANSL3	NM_001349256.2		c.1916A>G	p.Lys639Arg	missense	Exon 16 of 22	NP_001336185.1
	KANSL3	NM_001349257.2		c.1916A>G	p.Lys639Arg	missense	Exon 16 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.1838A>G	p.Lys613Arg	missense	Exon 15 of 21	ENSP00000396749.1	Q9P2N6-3
	KANSL3	ENST00000354204.10	TSL:1	n.*1680A>G		non_coding_transcript_exon	Exon 15 of 21	ENSP00000346144.7	F8WEN2
	KANSL3	ENST00000420155.5	TSL:1	n.1916A>G		non_coding_transcript_exon	Exon 16 of 21	ENSP00000414426.1	Q9P2N6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 6

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Benign	0.024
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.8
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.054
Sift	Uncertain	0.016	D
Sift4G	Benign	0.26	T
Polyphen		0.041	B
Vest4		0.15
MVP		0.22
MPC		0.69
ClinPred		0.72	D
GERP RS		4.9
gMVP		0.26
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200065186; hg19: chr2-97271152;