17-8466982-C-T

Variant names:

• chr17-8466982-C-T
• rs1428572494
• NM_030808.5:c.997C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_030808.5(NDEL1):​c.997C>T​(p.Arg333Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: NDEL1 NM_030808.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.07
• Publications: 1 publications found

Genes affected

NDEL1 (HGNC:17620): (nudE neurodevelopment protein 1 like 1) Enables identical protein binding activity. Involved in chromosome segregation; positive regulation of GTPase activity; and regulation of intracellular protein transport. Located in kinetochore. Biomarker of schizophrenia. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 27 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030808.5. 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
	NDEL1	NM_030808.5	MANE Select	c.997C>T	p.Arg333Cys	missense	Exon 9 of 9	NP_110435.1	Q9GZM8-1
	NDEL1	NM_001025579.3		c.*45C>T		3_prime_UTR	Exon 10 of 10	NP_001020750.1	Q9GZM8-3
	NDEL1	NM_001330129.2		c.*35C>T		3_prime_UTR	Exon 8 of 8	NP_001317058.1	A6NIZ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDEL1	ENST00000334527.12	TSL:1 MANE Select	c.997C>T	p.Arg333Cys	missense	Exon 9 of 9	ENSP00000333982.7	Q9GZM8-1
	NDEL1	ENST00000852241.1		c.1087C>T	p.Arg363Cys	missense	Exon 10 of 10	ENSP00000522300.1
	NDEL1	ENST00000852238.1		c.997C>T	p.Arg333Cys	missense	Exon 9 of 9	ENSP00000522297.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1461884 Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.094	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0045	T
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.1
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.015	D
Sift4G	Benign	0.068	T
Polyphen		1.0	D
Vest4		0.48
MutPred		0.70		Loss of methylation at R333 (P = 0.032)
MVP		0.79
MPC		1.4
ClinPred		0.91	D
GERP RS		4.5
Varity_R		0.11
gMVP		0.52
Mutation Taster		=84/16	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: rs1428572494; hg19: chr17-8370300;