NM_000111.3:c.2104_2105delGGinsACCGGTTTTGAAGTGAAAATTCAAAATTT

Variant names:

• chr7-107767866-CC-AAATTTTGAATTTTCACTTCAAAACCGGT
• rs386833472
• NM_000111.3:c.2104_2105delGGinsACCGGTTTTGAAGTGAAAATTCAAAATTT

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM4 PP5

The NM_000111.3(SLC26A3):​c.2104_2105delGGinsACCGGTTTTGAAGTGAAAATTCAAAATTT​(p.Gly702delinsThrGlyPheGluValLysIleGlnAsnPhe) variant causes a missense, conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC26A3 NM_000111.3 missense, conservative_inframe_insertion
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.42
• Publications: 0 publications found

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: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_000111.3.
• PP5: Variant 7-107767866-CC-AAATTTTGAATTTTCACTTCAAAACCGGT is Pathogenic according to our data. Variant chr7-107767866-CC-AAATTTTGAATTTTCACTTCAAAACCGGT is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 55990.Status of the report is no_assertion_criteria_provided, 0 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A3	NM_000111.3	MANE Select	c.2104_2105delGGinsACCGGTTTTGAAGTGAAAATTCAAAATTT	p.Gly702delinsThrGlyPheGluValLysIleGlnAsnPhe	missense conservative_inframe_insertion	N/A	NP_000102.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A3	ENST00000340010.10	TSL:1 MANE Select	c.2104_2105delGGinsACCGGTTTTGAAGTGAAAATTCAAAATTT	p.Gly702delinsThrGlyPheGluValLysIleGlnAsnPhe	missense conservative_inframe_insertion	N/A	ENSP00000345873.5
	SLC26A3	ENST00000379083.7	TSL:2	n.*1661_*1662delGGinsACCGGTTTTGAAGTGAAAATTCAAAATTT		non_coding_transcript_exon	Exon 18 of 20	ENSP00000368375.3
	SLC26A3	ENST00000379083.7	TSL:2	n.*1661_*1662delGGinsACCGGTTTTGAAGTGAAAATTCAAAATTT		3_prime_UTR	Exon 18 of 20	ENSP00000368375.3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Congenital secretory diarrhea, chloride type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4

Splicing

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

Other links and lift over

dbSNP: rs386833472; hg19: chr7-107408311;