chr3-48627947-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022911.3(SLC26A6):c.1892T>C(p.Met631Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000114 in 1,584,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

SLC26A6
NM_022911.3 missense, splice_region

Scores

Splicing: ADA: 0.000007307

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.203

Publications

1 publications found

Variant links:

Genes affected

SLC26A6 (HGNC:14472): (solute carrier family 26 member 6) This gene belongs to the solute carrier 26 family, whose members encode anion transporter proteins. This particular family member encodes a protein involved in transporting chloride, oxalate, sulfate and bicarbonate. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Aug 2013]

SLC26A6 links:

ENSG00000300190 (HGNC:):

ENSG00000300190 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08235896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A6	NM_022911.3 link	c.1892T>C	p.Met631Thr	missense_variant, splice_region_variant	Exon 17 of 21	ENST00000395550.7	NP_075062.2	Q9BXS9-1Q9Y3Y1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A6	ENST00000395550.7 link	c.1892T>C	p.Met631Thr	missense_variant, splice_region_variant	Exon 17 of 21	1	NM_022911.3	ENSP00000378920.2		Q9BXS9-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

GnomAD2 exomes

AF:

0.00000903

AC:

AN:

221550

AF XY:

0.0000164

show subpopulations

Gnomad AFR exome

AF:

0.0000720

Gnomad AMR exome

AF:

0.0000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000768

AC:

AN:

1432528

Hom.:

Cov.:

AF XY:

0.00000842

AC XY:

AN XY:

712882

show subpopulations

African (AFR)

AF:

0.000159

AC:

AN:

31354

American (AMR)

AF:

0.000136

AC:

AN:

36802

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25118

East Asian (EAS)

AF:

0.00

AC:

AN:

37702

South Asian (SAS)

AF:

0.00

AC:

AN:

81082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53244

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5672

European-Non Finnish (NFE)

AF:

9.07e-7

AC:

AN:

1102490

Other (OTH)

AF:

0.00

AC:

AN:

59064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

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:

0.0000460

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41440

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

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:

0.0000712

Hom.:

Bravo

AF:

0.0000529

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 05, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1892T>C (p.M631T) alteration is located in exon 17 (coding exon 17) of the SLC26A6 gene. This alteration results from a T to C substitution at nucleotide position 1892, causing the methionine (M) at amino acid position 631 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.33

CADD

Benign

0.99

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.0026

.;T;T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.36

T;T;T;T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.082

T;T;T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.34

N;.;N;.;.

PhyloP100

0.20

PROVEAN

Benign

0.24

N;N;N;N;N

REVEL

Benign

0.22

Sift

Benign

0.57

T;T;T;T;T

Sift4G

Benign

0.62

T;T;T;T;T

Polyphen

0.0010, 0.0090

.;.;B;B;.

Vest4

0.20

MutPred

0.39

Loss of catalytic residue at M631 (P = 0.0144);.;Loss of catalytic residue at M631 (P = 0.0144);.;.;

MVP

0.39

MPC

0.23

ClinPred

0.0071

GERP RS

0.93

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Varity_R

0.021

gMVP

0.17

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000073

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over