rs386833472

Positions:

• chr7-107767865-ACC-AAAATTTTGAATTTTCACTTCAAAACCGGT
• chr7-107767865-ACC-AC

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PS1 PM1 PM2 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. Variant has been reported in ClinVar as Likely pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin Lovd.

• 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

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]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PS1: Transcript NM_000111.3 (SLC26A3) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in Lovd
• PM1: In a domain STAS (size 195) in uniprot entity S26A3_HUMAN there are 6 pathogenic changes around while only 0 benign (100%) in NM_000111.3
• PM2: Very rare variant in population databases, with high coverage
• 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 id is 55990.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A3	NM_000111.3	c.2104_2105delGGinsACCGGTTTTGAAGTGAAAATTCAAAATTT	p.Gly702delinsThrGlyPheGluValLysIleGlnAsnPhe	missense_variant, conservative_inframe_insertion		ENST00000340010.10	NP_000102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A3	ENST00000340010.10	c.2104_2105delGGinsACCGGTTTTGAAGTGAAAATTCAAAATTT	p.Gly702delinsThrGlyPheGluValLysIleGlnAsnPhe	missense_variant, conservative_inframe_insertion		1	NM_000111.3	ENSP00000345873.5
SLC26A3	ENST00000379083.7	n.*1661_*1662delGGinsACCGGTTTTGAAGTGAAAATTCAAAATTT		non_coding_transcript_exon_variant	18/20	2		ENSP00000368375.3
SLC26A3	ENST00000379083.7	n.*1661_*1662delGGinsACCGGTTTTGAAGTGAAAATTCAAAATTT		3_prime_UTR_variant	18/20	2		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

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Congenital secretory diarrhea, chloride type Pathogenic:1

Likely pathogenic, no assertion criteria provided

literature only

Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs386833472; hg19: chr7-107408311;