rs3741628

Variant names:

• chr12-48654955-G-A
• rs3741628
• NM_017822.4:c.1333C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-48654955-G-A
• chr12-48654955-G-T

Variant summary

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

The NM_017822.4(KANSL2):​c.1333C>T​(p.Pro445Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: KANSL2 NM_017822.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228
• Publications: 47 publications found

Genes affected

KANSL2 (HGNC:26024): (KAT8 regulatory NSL complex subunit 2) Involved in histone H4-K16 acetylation; histone H4-K5 acetylation; and histone H4-K8 acetylation. Located in several cellular components, including actin cytoskeleton; cytosol; and 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=0.0741767).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANSL2	NM_017822.4	c.1333C>T	p.Pro445Ser	missense_variant	Exon 9 of 10	ENST00000420613.7	NP_060292.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANSL2	ENST00000420613.7	c.1333C>T	p.Pro445Ser	missense_variant	Exon 9 of 10	1	NM_017822.4	ENSP00000415436.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416700 Hom.: 0 Cov.: 40 AF XY: 0.00000143 AC XY: 1 AN XY: 700248

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32540

American (AMR) AF: 0.00 AC: 0 AN: 37316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25350

East Asian (EAS) AF: 0.00 AC: 0 AN: 37332

South Asian (SAS) AF: 0.00 AC: 0 AN: 80150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50874

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1088516

Other (OTH) AF: 0.00 AC: 0 AN: 58904

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.2
DANN	Benign	0.75
DEOGEN2	Benign	0.026	.;T;T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.065	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	.;N;.;.
PhyloP100		0.23
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Benign	0.031
Sift	Benign	0.078	T;T;T;T
Sift4G	Benign	0.18	T;T;T;T
Polyphen		0.041	B;B;.;B
Vest4		0.099
MutPred		0.31		Loss of loop (P = 0.0128);.;.;.;
MVP		0.35
MPC		0.35
ClinPred		0.18	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.025
gMVP		0.32
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3741628; hg19: chr12-49048738;