rs747600071

Variant names:

• chr17-8466970-C-A
• rs747600071
• NM_030808.5:c.985C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-8466970-C-A
• chr17-8466970-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030808.5(NDEL1):​c.985C>A​(p.Leu329Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NDEL1 NM_030808.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24014953).

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.985C>A	p.Leu329Met	missense	Exon 9 of 9	NP_110435.1	Q9GZM8-1
	NDEL1	NM_001025579.3		c.*33C>A		3_prime_UTR	Exon 10 of 10	NP_001020750.1	Q9GZM8-3
	NDEL1	NM_001330129.2		c.*23C>A		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.985C>A	p.Leu329Met	missense	Exon 9 of 9	ENSP00000333982.7	Q9GZM8-1
	NDEL1	ENST00000852241.1		c.1075C>A	p.Leu359Met	missense	Exon 10 of 10	ENSP00000522300.1
	NDEL1	ENST00000852238.1		c.985C>A	p.Leu329Met	missense	Exon 9 of 9	ENSP00000522297.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251364 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461882 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

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: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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	Benign	0.087
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.054	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.14	N
PhyloP100		1.4
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.16
Sift	Benign	0.33	T
Sift4G	Benign	0.24	T
Polyphen		0.97	D
Vest4		0.30
MutPred		0.40		Gain of methylation at R333 (P = 0.1805)
MVP		0.51
MPC		0.65
ClinPred		0.26	T
GERP RS		3.3
Varity_R		0.13
gMVP		0.23

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: rs747600071; hg19: chr17-8370288;