rs11800642

Positions:

• chr1-212736402-A-G
• chr1-212736402-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015471.4(NSL1):​c.*2006T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 984,278 control chromosomes in the GnomAD database, including 12,487 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2769 hom., cov: 33)
  • Exomes 𝑓: 0.15 (9718 hom.)
• Consequence: NSL1 NM_015471.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSL1	NM_015471.4	c.*2006T>C		3_prime_UTR_variant	6/6	ENST00000366977.8	NP_056286.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSL1	ENST00000366977.8	c.*2006T>C		3_prime_UTR_variant	6/6	1	NM_015471.4	ENSP00000355944	P1
NSL1	ENST00000366978.5	c.191-9223T>C		intron_variant		2		ENSP00000355945

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27237 AN: 151988 Hom.: 2760 Cov.: 33

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0997

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.188

GnomAD4 exome AF: 0.151 AC: 125612 AN: 832172 Hom.: 9718 Cov.: 24 AF XY: 0.150 AC XY: 57743 AN XY: 384292

Gnomad4 AFR exome AF: 0.290

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.129

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.179 AC: 27269 AN: 152106 Hom.: 2769 Cov.: 33 AF XY: 0.176 AC XY: 13097 AN XY: 74356

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.0997

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.186

Alfa AF: 0.142 Hom.: 1613

Bravo AF: 0.184

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.80
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11800642; hg19: chr1-212909744;