rs386833445

Positions:

• chr7-107783276-CAACCATTGCGATGCCGAA-CGGCATC

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1 PM2 PM4 PP3 PP5

The NM_000111.3(SLC26A3):​c.1030_1047delinsGATGCC​(p.Phe344_Val349delinsAspAla) variant causes a protein altering change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. F344F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC26A3 NM_000111.3 protein_altering
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.50

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 Likely_pathogenic. Variant got 8 ACMG points.

• PM1: In a transmembrane_region Helical (size 20) in uniprot entity S26A3_HUMAN there are 4 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.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 7-107783277-AACCATTGCGATGCCGAA-GGCATC is Pathogenic according to our data. Variant chr7-107783277-AACCATTGCGATGCCGAA-GGCATC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 55963.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A3	NM_000111.3	c.1030_1047delinsGATGCC	p.Phe344_Val349delinsAspAla	protein_altering_variant	9/21	ENST00000340010.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A3	ENST00000340010.10	c.1030_1047delinsGATGCC	p.Phe344_Val349delinsAspAla	protein_altering_variant	9/21	1	NM_000111.3	P1
SLC26A3	ENST00000468551.1	n.308_325delinsGATGCC		non_coding_transcript_exon_variant	3/5	2
SLC26A3	ENST00000379083.7	c.*821_*838delinsGATGCC		3_prime_UTR_variant, NMD_transcript_variant	9/20	2

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: rs386833445; hg19: chr7-107423722;