Genetic Variant NM_152519.4:c.2040T>C (chr2-210031536-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_152519.4(KANSL1L):c.2040T>C(p.Thr680Thr) variant causes a synonymous change. The variant allele was found at a frequency of 0.000313 in 1,539,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

KANSL1L
NM_152519.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.77

Variant links:

Genes affected

KANSL1L (HGNC:26310): (KAT8 regulatory NSL complex subunit 1 like) Predicted to enable histone acetyltransferase binding activity. Predicted to be part of NSL complex. [provided by Alliance of Genome Resources, Apr 2022]

KANSL1L links:

KANSL1L-AS1 (HGNC:41139): (KANSL1L antisense RNA 1)

KANSL1L-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 2-210031536-A-G is Benign according to our data. Variant chr2-210031536-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 735231.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANSL1L	NM_152519.4 link	c.2040T>C	p.Thr680Thr	synonymous_variant	Exon 9 of 15	ENST00000281772.14	NP_689732.2	A0AUZ9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KANSL1L	ENST00000281772.14 link	c.2040T>C	p.Thr680Thr	synonymous_variant	Exon 9 of 15	5	NM_152519.4	ENSP00000281772.8	A0AUZ9-1
KANSL1L	ENST00000418791.5 link	c.2030-1618T>C		intron_variant	Intron 8 of 13	1		ENSP00000405724.1	A0AUZ9-2
KANSL1L-AS1	ENST00000452057.1 link	n.775+29A>G		intron_variant	Intron 1 of 3	2
KANSL1L-AS1	ENST00000668130.1 link	n.936+29A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000114

AC:

AN:

236846

Hom.:

AF XY:

0.0000936

AC XY:

AN XY:

128186

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000324

AC:

450

AN:

1386908

Hom.:

Cov.:

AF XY:

0.000312

AC XY:

216

AN XY:

693330

show subpopulations

Gnomad4 AFR exome

AF:

0.0000964

Gnomad4 AMR exome

AF:

0.000101

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000412

Gnomad4 OTH exome

AF:

0.000138

GnomAD4 genome

AF:

0.000210

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000281

Hom.:

Bravo

AF:

0.000280

EpiCase

AF:

0.000383

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 02, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

9.3

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over