1-212736402-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015471.4(NSL1):​c.*2006T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000012 in 832,764 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000012 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSL1	NM_015471.4	MANE Select	c.*2006T>A		3_prime_UTR	Exon 6 of 6	NP_056286.3
	NSL1	NM_001297736.2		c.*2006T>A		3_prime_UTR	Exon 4 of 4	NP_001284665.1
	NSL1	NM_001042549.2		c.*2295T>A		3_prime_UTR	Exon 7 of 7	NP_001036014.1	Q96IY1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSL1	ENST00000366977.8	TSL:1 MANE Select	c.*2006T>A		3_prime_UTR	Exon 6 of 6	ENSP00000355944.3	Q96IY1-1
	NSL1	ENST00000935315.1		c.*2006T>A		3_prime_UTR	Exon 6 of 6	ENSP00000605374.1
	NSL1	ENST00000862262.1		c.*2006T>A		3_prime_UTR	Exon 4 of 4	ENSP00000532321.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000120 AC: 1 AN: 832764 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 384588

African (AFR) AF: 0.00 AC: 0 AN: 15776

American (AMR) AF: 0.00 AC: 0 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5150

East Asian (EAS) AF: 0.00 AC: 0 AN: 3630

South Asian (SAS) AF: 0.00 AC: 0 AN: 16450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1620

European-Non Finnish (NFE) AF: 0.00000131 AC: 1 AN: 761600

Other (OTH) AF: 0.00 AC: 0 AN: 27278

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2152

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.70
DANN	Benign	0.77
PhyloP100		-0.46

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;