Variant 1-43451930-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001190880.3(HYI):c.505+5G>A variant causes a splice donor 5th base, intron change. The variant allele was found at a frequency of 0.00262 in 1,612,544 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0071 ( 16 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 44 hom. )

Consequence

HYI
NM_001190880.3 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.9999

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.86

Variant links:

Genes affected

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]

SZT2 links:

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]

HYI links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 1-43451930-C-T is Benign according to our data. Variant chr1-43451930-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445670.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00706 (1074/152206) while in subpopulation SAS AF= 0.023 (111/4818). AF 95% confidence interval is 0.0196. There are 16 homozygotes in gnomad4. There are 525 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SZT2	NM_001365999.1 linkuse as main transcript	c.*1450C>T		3_prime_UTR_variant	72/72	ENST00000634258.3
HYI	NM_001190880.3 linkuse as main transcript	c.505+5G>A		splice_donor_5th_base_variant, intron_variant		ENST00000372430.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SZT2	ENST00000634258.3 linkuse as main transcript	c.*1450C>T		3_prime_UTR_variant	72/72	5	NM_001365999.1	P1	Q5T011-1
HYI	ENST00000372430.9 linkuse as main transcript	c.505+5G>A		splice_donor_5th_base_variant, intron_variant		1	NM_001190880.3	P1	Q5T013-1

Frequencies

GnomAD3 genomes

AF:

0.00699

AC:

1063

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0189

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0199

Gnomad SAS

AF:

0.0230

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00537

AC:

1346

AN:

250428

Hom.:

AF XY:

0.00565

AC XY:

765

AN XY:

135424

show subpopulations

Gnomad AFR exome

AF:

0.0209

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.000401

Gnomad EAS exome

AF:

0.0231

Gnomad SAS exome

AF:

0.0161

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00216

AC:

3152

AN:

1460338

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

1850

AN XY:

726214

show subpopulations

Gnomad4 AFR exome

AF:

0.0189

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.000652

Gnomad4 EAS exome

AF:

0.0152

Gnomad4 SAS exome

AF:

0.0164

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000141

Gnomad4 OTH exome

AF:

0.00416

GnomAD4 genome

AF:

0.00706

AC:

1074

AN:

152206

Hom.:

Cov.:

AF XY:

0.00706

AC XY:

525

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0191

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0200

Gnomad4 SAS

AF:

0.0230

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.0716

Hom.:

2354

Bravo

AF:

0.00740

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Aug 08, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.97

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.29

Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over