4-989824-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_022042.4(SLC26A1):c.1115G>A(p.Arg372His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,580,354 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 21 hom., cov: 35)

Exomes 𝑓: 0.011 ( 135 hom. )

Consequence

SLC26A1
NM_022042.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0440

Variant links:

Genes affected

SLC26A1 (HGNC:10993): (solute carrier family 26 member 1) This gene is a member of a family of sulfate/anion transporter genes. Family members are well conserved in their genomic (number and size of exons) and protein (aa length among species) structures, but have markedly different tissue expression patterns. This gene is primarily expressed in the liver, pancreas, and brain. Three splice variants that encode different isoforms have been identified. [provided by RefSeq, Jul 2008]

SLC26A1 links:

IDUA (HGNC:5391): (alpha-L-iduronidase) This gene encodes an enzyme that hydrolyzes the terminal alpha-L-iduronic acid residues of two glycosaminoglycans, dermatan sulfate and heparan sulfate. This hydrolysis is required for the lysosomal degradation of these glycosaminoglycans. Mutations in this gene that result in enzymatic deficiency lead to the autosomal recessive disease mucopolysaccharidosis type I (MPS I). [provided by RefSeq, Jul 2008]

IDUA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052942634).

BP6

Variant 4-989824-C-T is Benign according to our data. Variant chr4-989824-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 376863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00971 (1480/152368) while in subpopulation AMR AF= 0.0278 (426/15310). AF 95% confidence interval is 0.0256. There are 21 homozygotes in gnomad4. There are 736 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A1	NM_022042.4 link	c.1115G>A	p.Arg372His	missense_variant	Exon 3 of 3	ENST00000398516.3	NP_071325.2	Q9H2B4-1
IDUA	NM_000203.5 link	c.299+1875C>T		intron_variant	Intron 2 of 13	ENST00000514224.2	NP_000194.2	P35475-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A1	ENST00000398516.3 link	c.1115G>A	p.Arg372His	missense_variant	Exon 3 of 3	1	NM_022042.4	ENSP00000381528.2		Q9H2B4-1
IDUA	ENST00000514224.2 link	c.299+1875C>T		intron_variant	Intron 2 of 13	2	NM_000203.5	ENSP00000425081.2		P35475-1

Frequencies

GnomAD3 genomes

AF:

0.00972

AC:

1480

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0278

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.0209

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.0146

AC:

2818

AN:

192628

Hom.:

AF XY:

0.0127

AC XY:

1332

AN XY:

104506

show subpopulations

Gnomad AFR exome

AF:

0.00195

Gnomad AMR exome

AF:

0.0495

Gnomad ASJ exome

AF:

0.00359

Gnomad EAS exome

AF:

0.0000686

Gnomad SAS exome

AF:

0.00339

Gnomad FIN exome

AF:

0.0201

Gnomad NFE exome

AF:

0.0103

Gnomad OTH exome

AF:

0.0136

GnomAD4 exome

AF:

0.0106

AC:

15188

AN:

1427986

Hom.:

135

Cov.:

AF XY:

0.0103

AC XY:

7280

AN XY:

707202

show subpopulations

Gnomad4 AFR exome

AF:

0.00179

Gnomad4 AMR exome

AF:

0.0459

Gnomad4 ASJ exome

AF:

0.00423

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00364

Gnomad4 FIN exome

AF:

0.0227

Gnomad4 NFE exome

AF:

0.0103

Gnomad4 OTH exome

AF:

0.00904

GnomAD4 genome

AF:

0.00971

AC:

1480

AN:

152368

Hom.:

Cov.:

AF XY:

0.00988

AC XY:

736

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.0278

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.000577

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.0209

Gnomad4 NFE

AF:

0.0104

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00908

Hom.:

Bravo

AF:

0.0106

TwinsUK

AF:

0.0124

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00163

AC:

ESP6500EA

AF:

0.00866

AC:

ExAC

AF:

0.00995

AC:

1181

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 26, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 16, 2017

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nephrolithiasis, calcium oxalate

Benign:1

May 25, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Uncertain

0.56

D;D

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.87

.;D

MetaRNN

Benign

0.0053

T;T

MetaSVM

Uncertain

-0.26

MutationAssessor

Benign

1.7

L;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.21

Sift

Benign

0.088

T;T

Sift4G

Uncertain

0.018

D;D

Polyphen

0.24

B;B

Vest4

0.11

MPC

0.18

ClinPred

0.0051

GERP RS

3.4

Varity_R

0.057

gMVP

0.59

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

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