9-137040717-C-G

Variant names:

• chr9-137040717-C-G
• rs370154019
• NM_015392.4:c.577G>C

Variant summary

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

The NM_015392.4(NPDC1):​c.577G>C​(p.Val193Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NPDC1 NM_015392.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.577G>C	p.Val193Leu	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.577G>C	p.Val193Leu	missense	Exon 5 of 9	ENSP00000360660.4	Q9NQX5
	NPDC1	ENST00000371600.7	TSL:1	c.811G>C	p.Val271Leu	missense	Exon 4 of 8	ENSP00000360659.3	Q5SPY9
	NPDC1	ENST00000952624.1		c.577G>C	p.Val193Leu	missense	Exon 5 of 9	ENSP00000622683.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.3
DANN	Benign	0.63
DEOGEN2	Benign	0.19	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.68	N
PhyloP100		-0.65
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.041
Sift	Benign	0.31	T
Sift4G	Benign	0.32	T
Polyphen		0.0040	B
Vest4		0.18
MutPred		0.64		Loss of MoRF binding (P = 0.5059)
MVP		0.043
MPC		0.072
ClinPred		0.037	T
GERP RS		-0.30
PromoterAI		0.012	Neutral
Varity_R		0.029
gMVP		0.17
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: -13

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs370154019; hg19: chr9-139935169;