1-43452278-C-G

Variant names:

• chr1-43452278-C-G
• rs776997759
• NM_001190880.3:c.353G>C

Variant summary

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

The NM_001190880.3(HYI):​c.353G>C​(p.Arg118Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R118Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HYI NM_001190880.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.69

Genes affected

HYI (HGNC:26948): (hydroxypyruvate isomerase (putative)) This gene encodes a putative hydroxypyruvate isomerase, which likely catalyzes the conversion of hydroxypyruvate to 2-hydroxy-3-oxopropanoate, and may be involved in carbohydrate transport and metabolism. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

SZT2 (HGNC:29040): (SZT2 subunit of KICSTOR complex) The protein encoded by this gene is expressed in the brain, predominantly in the parietal and frontal cortex as well as in dorsal root ganglia. It is localized to the peroxisome, and is implicated in resistance to oxidative stress. It likely functions by increasing superoxide dismutase (SOD) activity, but itself has no direct SOD activity. Studies in mice show that this gene confers low seizure threshold, and may also enhance epileptogenesis. [provided by RefSeq, Jun 2011]

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=0.23382929).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYI	NM_001190880.3	c.353G>C	p.Arg118Pro	missense_variant	Exon 3 of 8	ENST00000372430.9	NP_001177809.1
SZT2	NM_001365999.1	c.*1798C>G		3_prime_UTR_variant	Exon 72 of 72	ENST00000634258.3	NP_001352928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYI	ENST00000372430.9	c.353G>C	p.Arg118Pro	missense_variant	Exon 3 of 8	1	NM_001190880.3	ENSP00000361507.4
SZT2	ENST00000634258.3	c.*1798C>G		3_prime_UTR_variant	Exon 72 of 72	5	NM_001365999.1	ENSP00000489255.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250836 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135566

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	17
DANN	Benign	0.78
DEOGEN2	Benign	0.27	T;T;T;.;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.73
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.76	T;T;T;T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.23	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L;.;.;L;.
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.2	D;.;.;D;D
REVEL	Benign	0.27
Sift	Benign	0.13	T;.;.;T;T
Sift4G	Benign	0.11	T;D;T;D;T
Polyphen		0.028	B;.;.;.;.
Vest4		0.43
MutPred		0.55		Loss of MoRF binding (P = 9e-04);.;.;Loss of MoRF binding (P = 9e-04);Loss of MoRF binding (P = 9e-04);
MVP		0.37
MPC		0.088
ClinPred		0.12	T
GERP RS		1.4
Varity_R		0.46
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs776997759; hg19: chr1-43917949;