1-246758314-A-G

Position:

• chr1-246758314-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016002.3(SCCPDH):​c.653A>G​(p.Asn218Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SCCPDH NM_016002.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08485636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCCPDH	NM_016002.3	c.653A>G	p.Asn218Ser	missense_variant	6/12	ENST00000366510.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCCPDH	ENST00000366510.4	c.653A>G	p.Asn218Ser	missense_variant	6/12	1	NM_016002.3	P1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 28

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74370

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	4.8
DANN	Benign	0.58
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.059
Sift	Benign	0.38	T
Sift4G	Benign	0.40	T
Polyphen		0.036	B
Vest4		0.13
MutPred		0.35		Gain of loop (P = 0.0045);
MVP		0.48
MPC		0.12
ClinPred		0.085	T
GERP RS		0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.016
gMVP		0.54

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

LitVar

Other links and lift over

dbSNP: rs1396632535; hg19: chr1-246921616;