12-122598915-T-A

Variant names:

• chr12-122598915-T-A
• rs11058879
• NM_014708.6:c.4563+977T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014708.6(KNTC1):​c.4563+977T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 152,006 control chromosomes in the GnomAD database, including 15 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 0.011 (15 hom., cov: 31)
• Consequence: KNTC1 NM_014708.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513
• Publications: 0 publications found

Genes affected

KNTC1 (HGNC:17255): (kinetochore associated 1) This gene encodes a protein that is one of many involved in mechanisms to ensure proper chromosome segregation during cell division. Experimental evidence indicated that the encoded protein functioned in a similar manner to that of the Drosophila rough deal protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0112 (1701/152006) while in subpopulation NFE AF = 0.0177 (1200/67974). AF 95% confidence interval is 0.0168. There are 15 homozygotes in GnomAd4. There are 843 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014708.6. 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
	KNTC1	NM_014708.6	MANE Select	c.4563+977T>A		intron	N/A	NP_055523.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KNTC1	ENST00000333479.12	TSL:1 MANE Select	c.4563+977T>A		intron	N/A	ENSP00000328236.6
	KNTC1	ENST00000450485.6	TSL:2	c.2272-10469T>A		intron	N/A	ENSP00000397992.2
	KNTC1	ENST00000423927.2	TSL:4	c.240+977T>A		intron	N/A	ENSP00000397140.2

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1700 AN: 151888 Hom.: 15 Cov.: 31

Gnomad AFR AF: 0.00271

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.0250

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.00959

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0112 AC: 1701 AN: 152006 Hom.: 15 Cov.: 31 AF XY: 0.0113 AC XY: 843 AN XY: 74328

African (AFR) AF: 0.00270 AC: 112 AN: 41468

American (AMR) AF: 0.00308 AC: 47 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.0116 AC: 56 AN: 4816

European-Finnish (FIN) AF: 0.0250 AC: 263 AN: 10538

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0177 AC: 1200 AN: 67974

Other (OTH) AF: 0.00949 AC: 20 AN: 2108

Alfa AF: 0.0151 Hom.: 4

Bravo AF: 0.00884

Asia WGS AF: 0.00491 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.56
DANN	Benign	0.45
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11058879; hg19: chr12-123083462;