rs200102493

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP2BP4_Strong

The NM_000441.2(SLC26A4):c.28C>A(p.Pro10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,570,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). The gene SLC26A4 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

SLC26A4
NM_000441.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:8B:1

Conservation

PhyloP100: 1.56

Publications

1 publications found

Variant links:

Genes affected

SLC26A4 (HGNC:8818): (solute carrier family 26 member 4) Mutations in this gene are associated with Pendred syndrome, the most common form of syndromic deafness, an autosomal-recessive disease. It is highly homologous to the SLC26A3 gene; they have similar genomic structures and this gene is located 3' of the SLC26A3 gene. The encoded protein has homology to sulfate transporters. [provided by RefSeq, Jul 2008]

SLC26A4 links:

SLC26A4-AS1 (HGNC:22385): (SLC26A4 antisense RNA 1)

SLC26A4-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000441.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Specifications for SLC26A4 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 167 curated pathogenic missense variants (we use a threshold of 10). The gene has 19 curated benign missense variants. Trascript score misZ: -1.7621 (below the threshold of 3.09). GenCC associations: The gene is linked to hearing loss, autosomal recessive, Pendred syndrome, autosomal recessive nonsyndromic hearing loss 4, thyroid hypoplasia, athyreosis.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062066913).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000441.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A4	NM_000441.2	MANE Select	c.28C>A	p.Pro10Thr	missense	Exon 2 of 21	NP_000432.1	O43511-1
	SLC26A4-AS1	NR_028137.1		n.130G>T		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC26A4	ENST00000644269.2	MANE Select	c.28C>A	p.Pro10Thr	missense	Exon 2 of 21	ENSP00000494017.1	O43511-1
SLC26A4	ENST00000888701.1		c.28C>A	p.Pro10Thr	missense	Exon 1 of 20	ENSP00000558760.1
SLC26A4	ENST00000888700.1		c.28C>A	p.Pro10Thr	missense	Exon 2 of 20	ENSP00000558759.1

Frequencies

GnomAD3 genomes

AF:

0.000663

AC:

101

AN:

152274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00231

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000160

AC:

AN:

181450

AF XY:

0.000101

show subpopulations

Gnomad AFR exome

AF:

0.00217

Gnomad AMR exome

AF:

0.000176

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000709

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000125

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000508

AC:

AN:

1417634

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

702236

show subpopulations

African (AFR)

AF:

0.00177

AC:

AN:

32794

American (AMR)

AF:

0.000178

AC:

AN:

39368

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25504

East Asian (EAS)

AF:

0.00

AC:

AN:

37914

South Asian (SAS)

AF:

0.00

AC:

AN:

81424

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41034

Middle Eastern (MID)

AF:

0.000360

AC:

AN:

5560

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1095062

Other (OTH)

AF:

0.0000848

AC:

AN:

58974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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

AF:

0.000669

AC:

102

AN:

152392

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74526

show subpopulations

African (AFR)

AF:

0.00233

AC:

AN:

41602

American (AMR)

AF:

0.000196

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000748

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Pendred syndrome (3)

Autosomal recessive nonsyndromic hearing loss 4 (1)

SLC26A4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.040

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.12

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.73

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.0062

MetaSVM

Benign

-0.45

MutationAssessor

Benign

0.0

PhyloP100

1.6

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.0

REVEL

Uncertain

0.52

Sift

Benign

0.29

Sift4G

Benign

0.23

Varity_R

0.056

gMVP

0.52

Mutation Taster

=74/26

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over