Genetic Variant NM_016002.3:c.145C>T (chr1-246724567-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_016002.3(SCCPDH):c.145C>T(p.Arg49Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,534,906 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

SCCPDH
NM_016002.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

Publications

1 publications found

Variant links:

Genes affected

SCCPDH (HGNC:24275): (saccharopine dehydrogenase (putative)) Predicted to enable oxidoreductase activity. Predicted to be involved in glycolipid biosynthetic process. Located in lipid droplet and midbody. [provided by Alliance of Genome Resources, Apr 2022]

SCCPDH links:

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ACMG classification

Classification was made for transcript

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_016002.3. 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
	SCCPDH	NM_016002.3	MANE Select	c.145C>T	p.Arg49Trp	missense	Exon 1 of 12	NP_057086.2	A0A384NPM7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCCPDH	ENST00000366510.4	TSL:1 MANE Select	c.145C>T	p.Arg49Trp	missense	Exon 1 of 12	ENSP00000355467.3	Q8NBX0
SCCPDH	ENST00000878248.1		c.145C>T	p.Arg49Trp	missense	Exon 1 of 12	ENSP00000548307.1
SCCPDH	ENST00000878244.1		c.145C>T	p.Arg49Trp	missense	Exon 1 of 12	ENSP00000548303.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

131542

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1382750

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

683168

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28706

American (AMR)

AF:

0.00

AC:

AN:

33506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24164

East Asian (EAS)

AF:

0.00

AC:

AN:

33084

South Asian (SAS)

AF:

0.00

AC:

AN:

78110

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48182

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4246

European-Non Finnish (NFE)

AF:

0.0000316

AC:

AN:

1075504

Other (OTH)

AF:

0.00

AC:

AN:

57248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.33

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.80

M_CAP

Pathogenic

0.73

MetaRNN

Uncertain

0.65

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.5

PhyloP100

1.1

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.18

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.33

MutPred

0.41

Loss of disorder (P = 0.002)

MVP

0.64

MPC

2.3

ClinPred

0.99

GERP RS

2.5

PromoterAI

-0.037

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.37

gMVP

0.59

Mutation Taster

=80/20

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over