rs1250484528

Variant names:

• chr1-246724507-C-G
• rs1250484528
• NM_016002.3:c.85C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-246724507-C-G
• chr1-246724507-C-T

Variant summary

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

The NM_016002.3(SCCPDH):​c.85C>G​(p.Arg29Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,419,662 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R29W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SCCPDH NM_016002.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21
• Publications: 0 publications found

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]

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_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.85C>G	p.Arg29Gly	missense	Exon 1 of 12	NP_057086.2	A0A384NPM7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCCPDH	ENST00000366510.4	TSL:1 MANE Select	c.85C>G	p.Arg29Gly	missense	Exon 1 of 12	ENSP00000355467.3	Q8NBX0
	SCCPDH	ENST00000878248.1		c.85C>G	p.Arg29Gly	missense	Exon 1 of 12	ENSP00000548307.1
	SCCPDH	ENST00000878244.1		c.85C>G	p.Arg29Gly	missense	Exon 1 of 12	ENSP00000548303.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1419662 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 703564

African (AFR) AF: 0.00 AC: 0 AN: 30420

American (AMR) AF: 0.00 AC: 0 AN: 38786

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24852

East Asian (EAS) AF: 0.00 AC: 0 AN: 36402

South Asian (SAS) AF: 0.00 AC: 0 AN: 81088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4702

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1094316

Other (OTH) AF: 0.00 AC: 0 AN: 58754

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.86	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		2.2
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.27
Sift	Benign	0.047	D
Sift4G	Benign	0.091	T
Polyphen		0.99	D
Vest4		0.25
MutPred		0.54		Loss of helix (P = 0.079)
MVP		0.69
MPC		1.7
ClinPred		0.99	D
GERP RS		3.4
PromoterAI		0.055	Neutral
Varity_R		0.65
gMVP		0.70
Mutation Taster		=55/45	polymorphism

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: rs1250484528; hg19: chr1-246887809;