rs11800642

Variant names:

• chr1-212736402-A-G
• rs11800642
• NM_015471.4:c.*2006T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015471.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSL1	NM_015471.4	MANE Select	c.*2006T>C		3_prime_UTR	Exon 6 of 6	NP_056286.3
	NSL1	NM_001297736.2		c.*2006T>C		3_prime_UTR	Exon 4 of 4	NP_001284665.1
	NSL1	NM_001042549.2		c.*2295T>C		3_prime_UTR	Exon 7 of 7	NP_001036014.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSL1	ENST00000366977.8	TSL:1 MANE Select	c.*2006T>C		3_prime_UTR	Exon 6 of 6	ENSP00000355944.3
	NSL1	ENST00000366978.5	TSL:2	c.191-9223T>C		intron	N/A	ENSP00000355945.1

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

African (AFR) AF: 0.290 AC: 4576 AN: 15764

American (AMR) AF: 0.114 AC: 112 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 565 AN: 5150

East Asian (EAS) AF: 0.129 AC: 466 AN: 3626

South Asian (SAS) AF: 0.151 AC: 2483 AN: 16434

European-Finnish (FIN) AF: 0.120 AC: 33 AN: 276

Middle Eastern (MID) AF: 0.131 AC: 213 AN: 1620

European-Non Finnish (NFE) AF: 0.148 AC: 112966 AN: 761048

Other (OTH) AF: 0.154 AC: 4198 AN: 27270

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

African (AFR) AF: 0.285 AC: 11834 AN: 41454

American (AMR) AF: 0.123 AC: 1881 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 392 AN: 3472

East Asian (EAS) AF: 0.141 AC: 730 AN: 5176

South Asian (SAS) AF: 0.156 AC: 752 AN: 4818

European-Finnish (FIN) AF: 0.0997 AC: 1054 AN: 10576

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10105 AN: 67992

Other (OTH) AF: 0.186 AC: 392 AN: 2112

Alfa AF: 0.145 Hom.: 2152

Bravo AF: 0.184

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.80
DANN	Benign	0.77
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11800642; hg19: chr1-212909744;