17-8450948-C-G

Variant names:

• chr17-8450948-C-G
• rs144719475
• NM_030808.5:c.695C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030808.5(NDEL1):​c.695C>G​(p.Pro232Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,584 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P232L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NDEL1 NM_030808.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3253271).

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.695C>G	p.Pro232Arg	missense	Exon 6 of 9	NP_110435.1	Q9GZM8-1
	NDEL1	NM_001025579.3		c.695C>G	p.Pro232Arg	missense	Exon 6 of 10	NP_001020750.1	Q9GZM8-3
	NDEL1	NM_001330129.2		c.695C>G	p.Pro232Arg	missense	Exon 6 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.695C>G	p.Pro232Arg	missense	Exon 6 of 9	ENSP00000333982.7	Q9GZM8-1
	NDEL1	ENST00000852241.1		c.695C>G	p.Pro232Arg	missense	Exon 6 of 10	ENSP00000522300.1
	NDEL1	ENST00000852238.1		c.695C>G	p.Pro232Arg	missense	Exon 6 of 9	ENSP00000522297.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455584 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724092

African (AFR) AF: 0.00 AC: 0 AN: 32970

American (AMR) AF: 0.00 AC: 0 AN: 42936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25962

East Asian (EAS) AF: 0.00 AC: 0 AN: 39424

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110006

Other (OTH) AF: 0.00 AC: 0 AN: 60144

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		1.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.051	T
Polyphen		0.38	B
Vest4		0.43
MutPred		0.69		Loss of ubiquitination at K233 (P = 0.0234)
MVP		0.31
MPC		1.0
ClinPred		0.94	D
GERP RS		5.0
PromoterAI		-0.022	Neutral
Varity_R		0.29
gMVP		0.62

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: rs144719475; hg19: chr17-8354266;