rs138330772

Variant names:

• chr9-137040702-C-A
• rs138330772
• NM_015392.4:c.592G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-137040702-C-A
• chr9-137040702-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015392.4(NPDC1):​c.592G>T​(p.Ala198Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. A198T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: NPDC1 NM_015392.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 0 publications found

Genes affected

NPDC1 (HGNC:7899): (neural proliferation, differentiation and control 1) Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.869

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015392.4. 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
	NPDC1	NM_015392.4	MANE Select	c.592G>T	p.Ala198Ser	missense	Exon 5 of 9	NP_056207.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPDC1	ENST00000371601.5	TSL:1 MANE Select	c.592G>T	p.Ala198Ser	missense	Exon 5 of 9	ENSP00000360660.4	Q9NQX5
	NPDC1	ENST00000371600.7	TSL:1	c.826G>T	p.Ala276Ser	missense	Exon 4 of 8	ENSP00000360659.3	Q5SPY9
	NPDC1	ENST00000952624.1		c.592G>T	p.Ala198Ser	missense	Exon 5 of 9	ENSP00000622683.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434158 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 711926

African (AFR) AF: 0.00 AC: 0 AN: 33376

American (AMR) AF: 0.00 AC: 0 AN: 40878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25564

East Asian (EAS) AF: 0.00 AC: 0 AN: 38948

South Asian (SAS) AF: 0.00 AC: 0 AN: 83082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42958

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

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103926

Other (OTH) AF: 0.00 AC: 0 AN: 59680

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.69	D
Eigen	Benign	0.016
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.2
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.78		Gain of glycosylation at A276 (P = 0.0332)
MVP		0.26
MPC		0.38
ClinPred		0.93	D
GERP RS		2.9
PromoterAI		-0.0014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.19
gMVP		0.24
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs138330772; hg19: chr9-139935154; COSMIC: COSV107388856; COSMIC: COSV107388856;