Genetic Variant NM_022042.4:c.*878G>T (chr4-987955-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022042.4(SLC26A1):c.*878G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000353 in 1,414,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

SLC26A1
NM_022042.4 3_prime_UTR

Scores

Splicing: ADA: 0.00007202

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

mucopolysaccharidosis type 1
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Myriad Women’s Health
Scheie syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Orphanet
Hurler syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia
Hurler-Scheie syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet

IDUA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A1	NM_022042.4 link	c.*878G>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000398516.3	NP_071325.2	Q9H2B4-1
IDUA	NM_000203.5 link	c.299+6C>A		splice_region_variant, 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.*878G>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_022042.4	ENSP00000381528.2		Q9H2B4-1
IDUA	ENST00000514224.2 link	c.299+6C>A		splice_region_variant, intron_variant	Intron 2 of 13	2	NM_000203.5	ENSP00000425081.2		P35475-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000353

AC:

AN:

1414688

Hom.:

Cov.:

AF XY:

0.00000572

AC XY:

AN XY:

699234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32258

American (AMR)

AF:

0.00

AC:

AN:

38266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25368

East Asian (EAS)

AF:

0.00

AC:

AN:

36996

South Asian (SAS)

AF:

0.00

AC:

AN:

81154

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48806

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5360

European-Non Finnish (NFE)

AF:

0.00000460

AC:

AN:

1087970

Other (OTH)

AF:

0.00

AC:

AN:

58510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

9.5

(source)

DANN

Benign

0.70

PhyloP100

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000072

dbscSNV1_RF

Benign

0.086

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.24

Position offset: -44

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over