Genetic Variant SLC26A3:p.Val318del (chr7-107786844-AACC-A) – ACMG Classification: Pathogenic (11 pts)

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PM2PM4_SupportingPP5_Very_Strong

The NM_000111.3(SLC26A3):c.951_953delGGT(p.Val318del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000204 in 1,613,956 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

SLC26A3
NM_000111.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, multiple submitters, no conflicts P:6

Conservation

PhyloP100: 7.48

Publications

6 publications found

Variant links:

Genes affected

SLC26A3 (HGNC:3018): (solute carrier family 26 member 3) The protein encoded by this gene is a transmembrane glycoprotein that transports chloride ions across the cell membrane in exchange for bicarbonate ions. It is localized to the mucosa of the lower intestinal tract, particularly to the apical membrane of columnar epithelium and some goblet cells. The protein is essential for intestinal chloride absorption, and mutations in this gene have been associated with congenital chloride diarrhea. [provided by RefSeq, Oct 2008]

SLC26A3 Gene-Disease associations (from GenCC):

congenital secretory chloride diarrhea 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia

SLC26A3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_000111.3. Strenght limited to Supporting due to length of the change: 1aa.

PP5

Variant 7-107786844-AACC-A is Pathogenic according to our data. Variant chr7-107786844-AACC-A is described in ClinVar as Pathogenic. ClinVar VariationId is 16754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000111.3. 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
	SLC26A3	NM_000111.3	MANE Select	c.951_953delGGT	p.Val318del	disruptive_inframe_deletion	Exon 8 of 21	NP_000102.1	P40879

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC26A3	ENST00000340010.10	TSL:1 MANE Select	c.951_953delGGT	p.Val318del	disruptive_inframe_deletion	Exon 8 of 21	ENSP00000345873.5	P40879
SLC26A3	ENST00000852261.1		c.951_953delGGT	p.Val318del	disruptive_inframe_deletion	Exon 8 of 21	ENSP00000522320.1
SLC26A3	ENST00000852262.1		c.951_953delGGT	p.Val318del	disruptive_inframe_deletion	Exon 8 of 21	ENSP00000522321.1

Frequencies

GnomAD3 genomes

AF:

0.000375

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00527

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000473

AC:

119

AN:

251340

AF XY:

0.000427

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00532

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000187

AC:

273

AN:

1461664

Hom.:

AF XY:

0.000166

AC XY:

121

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00491

AC:

262

AN:

53386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111864

Other (OTH)

AF:

0.000116

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.411

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:

0.000374

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41568

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00527

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2114

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:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital secretory diarrhea, chloride type (5)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

7.5

Mutation Taster

=63/37

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over