17-8448557-A-G

Variant names:

• chr17-8448557-A-G
• rs370477079
• NM_030808.5:c.397A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_030808.5(NDEL1):​c.397A>G​(p.Ile133Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,612,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: NDEL1 NM_030808.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.28
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15451428).
• BS2: High AC in GnomAd4 at 7 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.397A>G	p.Ile133Val	missense	Exon 5 of 9	NP_110435.1	Q9GZM8-1
	NDEL1	NM_001025579.3		c.397A>G	p.Ile133Val	missense	Exon 5 of 10	NP_001020750.1	Q9GZM8-3
	NDEL1	NM_001330129.2		c.397A>G	p.Ile133Val	missense	Exon 5 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.397A>G	p.Ile133Val	missense	Exon 5 of 9	ENSP00000333982.7	Q9GZM8-1
	NDEL1	ENST00000852241.1		c.397A>G	p.Ile133Val	missense	Exon 5 of 10	ENSP00000522300.1
	NDEL1	ENST00000852238.1		c.397A>G	p.Ile133Val	missense	Exon 5 of 9	ENSP00000522297.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152240 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000280 AC: 7 AN: 250056 AF XY: 0.0000148

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000294

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1459986 Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13 AN XY: 726214

African (AFR) AF: 0.0000600 AC: 2 AN: 33332

American (AMR) AF: 0.0000226 AC: 1 AN: 44278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39660

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111038

Other (OTH) AF: 0.0000166 AC: 1 AN: 60304

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152240 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74386

African (AFR) AF: 0.000121 AC: 5 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000986 Hom.: 0

Bravo AF: 0.0000453

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.0000546

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

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	Benign	0.22
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.026
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.3
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.057
Sift	Benign	0.18	T
Sift4G	Benign	0.67	T
Polyphen		0.027	B
Vest4		0.46
MVP		0.27
MPC		0.37
ClinPred		0.18	T
GERP RS		4.8
PromoterAI		0.037	Neutral
Varity_R		0.32
gMVP		0.22
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs370477079; hg19: chr17-8351875;