rs13381300

Positions:

• chr18-2572096-T-G

Variant summary

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

The NM_006101.3(NDC80):​c.-10+413T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0946 in 152,164 control chromosomes in the GnomAD database, including 949 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 0.095 (949 hom., cov: 33)
• Consequence: NDC80 NM_006101.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324

Genes affected

NDC80 (HGNC:16909): (NDC80 kinetochore complex component) This gene encodes a component of the NDC80 kinetochore complex. The encoded protein consists of an N-terminal microtubule binding domain and a C-terminal coiled-coiled domain that interacts with other components of the complex. This protein functions to organize and stabilize microtubule-kinetochore interactions and is required for proper chromosome segregation. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDC80	NM_006101.3	c.-10+413T>G		intron_variant		ENST00000261597.9	NP_006092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDC80	ENST00000261597.9	c.-10+413T>G		intron_variant		1	NM_006101.3	ENSP00000261597	P1
NDC80	ENST00000575515.1	c.-10+413T>G		intron_variant		5		ENSP00000461227

Frequencies

GnomAD3 genomes AF: 0.0946 AC: 14377 AN: 152046 Hom.: 947 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0660

Gnomad ASJ AF: 0.0692

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0429

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0667

Gnomad OTH AF: 0.0963

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

GnomAD4 genome AF: 0.0946 AC: 14394 AN: 152164 Hom.: 949 Cov.: 33 AF XY: 0.0908 AC XY: 6757 AN XY: 74382

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.0659

Gnomad4 ASJ AF: 0.0692

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0427

Gnomad4 FIN AF: 0.0202

Gnomad4 NFE AF: 0.0667

Gnomad4 OTH AF: 0.0962

Alfa AF: 0.0706 Hom.: 537

Bravo AF: 0.101

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.35

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

Other links and lift over

dbSNP: rs13381300; hg19: chr18-2572095;