chr1-246758287-A-C

Variant names:

• chr1-246758287-A-C
• rs1668960838
• NM_016002.3:c.626A>C

Variant summary

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

The NM_016002.3(SCCPDH):​c.626A>C​(p.Asn209Thr) 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 1,458,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: SCCPDH NM_016002.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.764
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.125969).

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.626A>C	p.Asn209Thr	missense	Exon 6 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.626A>C	p.Asn209Thr	missense	Exon 6 of 12	ENSP00000355467.3	Q8NBX0
	SCCPDH	ENST00000878248.1		c.626A>C	p.Asn209Thr	missense	Exon 6 of 12	ENSP00000548307.1
	SCCPDH	ENST00000878244.1		c.626A>C	p.Asn209Thr	missense	Exon 6 of 12	ENSP00000548303.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458762 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 725804

African (AFR) AF: 0.00 AC: 0 AN: 33352

American (AMR) AF: 0.00 AC: 0 AN: 44268

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39496

South Asian (SAS) AF: 0.00 AC: 0 AN: 85844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110308

Other (OTH) AF: 0.0000166 AC: 1 AN: 60256

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

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	0.092
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.9
DANN	Benign	0.96
DEOGEN2	Benign	0.068	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.76
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.070
Sift	Benign	0.12	T
Sift4G	Benign	0.092	T
Polyphen		0.0010	B
Vest4		0.16
MutPred		0.50		Gain of phosphorylation at N209 (P = 0.0774)
MVP		0.12
MPC		0.15
ClinPred		0.076	T
GERP RS		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.050
gMVP		0.51
Mutation Taster		=88/12	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: rs1668960838; hg19: chr1-246921589;