Variant 1-212791668-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_015471.4(NSL1):c.96C>A(p.Pro32Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000328 in 1,613,986 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 2 hom. )

Consequence

NSL1
NM_015471.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.874

Variant links:

Genes affected

NSL1 (HGNC:24548): (NSL1 component of MIS12 kinetochore complex) This gene encodes a protein with two coiled-coil domains that localizes to kinetochores, which are chromosome-associated structures that attach to microtubules and mediate chromosome movements during cell division. The encoded protein is part of a conserved protein complex that includes two chromodomain-containing proteins and a component of the outer plate of the kinetochore. This protein complex is proposed to bridge centromeric heterochromatin with the outer kinetochore structure. Multiple transcript variants encoding different isoforms have been found for this gene. There is a pseudogene of the 3' UTR region of this gene on chromosome X. [provided by RefSeq, Jul 2014]

NSL1 links:

NSL1 (HGNC:):

NSL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-212791668-G-T is Benign according to our data. Variant chr1-212791668-G-T is described in ClinVar as [Benign]. Clinvar id is 709035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.874 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSL1	NM_015471.4 linkuse as main transcript	c.96C>A	p.Pro32Pro	synonymous_variant	1/6	ENST00000366977.8	NP_056286.3	Q96IY1-1Q53FM2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NSL1	ENST00000366977.8 linkuse as main transcript	c.96C>A	p.Pro32Pro	synonymous_variant	1/6	1	NM_015471.4	ENSP00000355944.3	Q96IY1-1
NSL1	ENST00000626725.1 linkuse as main transcript	c.96C>A	p.Pro32Pro	synonymous_variant	1/7	2		ENSP00000486783.1	Q96IY1-2
NSL1	ENST00000366976.3 linkuse as main transcript	c.96C>A	p.Pro32Pro	synonymous_variant	1/5	2		ENSP00000355943.1	Q5SY74
NSL1	ENST00000487995.1 linkuse as main transcript	n.115C>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

209

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00391

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000479

AC:

120

AN:

250520

Hom.:

AF XY:

0.000354

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.00401

Gnomad AMR exome

AF:

0.00104

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:

0.000124

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.000220

AC:

321

AN:

1461714

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

153

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.00379

Gnomad4 AMR exome

AF:

0.00105

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:

0.0000809

Gnomad4 OTH exome

AF:

0.000596

GnomAD4 genome

AF:

0.00137

AC:

209

AN:

152272

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00390

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.00166

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

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