5-473394-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_004174.4(SLC9A3):c.2502-12C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000319 in 1,254,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: SLC9A3 NM_004174.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002383
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.83

Genes affected

SLC9A3 (HGNC:11073): (solute carrier family 9 member A3) The protein encoded by this gene is an epithelial brush border Na/H exchanger that uses an inward sodium ion gradient to expel acids from the cell. Defects in this gene are a cause of congenital secretory sodium diarrhea. Pseudogenes of this gene exist on chromosomes 10 and 22. [provided by RefSeq, Mar 2016]

SLC9A3-AS1 (HGNC:40550): (SLC9A3 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-473394-G-A is Benign according to our data. Variant chr5-473394-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1923367.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9A3	NM_004174.4	c.2502-12C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000264938.8
SLC9A3-AS1	NR_125375.1	n.159G>A		non_coding_transcript_exon_variant	1/7
SLC9A3	NM_001284351.3	c.2475-12C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9A3	ENST00000264938.8	c.2502-12C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004174.4	P2
SLC9A3	ENST00000514375.1	c.2475-12C>T		splice_polypyrimidine_tract_variant, intron_variant		1
SLC9A3-AS1	ENST00000607286.5	n.159G>A		non_coding_transcript_exon_variant	1/7	5
SLC9A3	ENST00000644203.1	c.2252-12C>T		splice_polypyrimidine_tract_variant, intron_variant				A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000319 AC: 4 AN: 1254196 Hom.: 0 Cov.: 31 AF XY: 0.00000162 AC XY: 1 AN XY: 617660

Gnomad4 AFR exome AF: 0.000116

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.96e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 23, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	7.3
Dann	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000024
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1436675643; hg19: chr5-473509;