5-473291-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_004174.4(SLC9A3):c.*88G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,308,852 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 34)
  • Exomes 𝑓: 0.0016 (14 hom.)
• Consequence: SLC9A3 NM_004174.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0210

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0058196783).
• BP6: Variant 5-473291-C-G is Benign according to our data. Variant chr5-473291-C-G is described in ClinVar as [Benign]. Clinvar id is 2655249.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00319 (483/151336) while in subpopulation AMR AF= 0.00762 (116/15226). AF 95% confidence interval is 0.00649. There are 1 homozygotes in gnomad4. There are 248 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9A3	NM_004174.4	c.*88G>C		3_prime_UTR_variant	17/17	ENST00000264938.8
SLC9A3-AS1	NR_125375.1	n.56C>G		non_coding_transcript_exon_variant	1/7
SLC9A3	NM_001284351.3	c.*88G>C		3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9A3	ENST00000264938.8	c.*88G>C		3_prime_UTR_variant	17/17	1	NM_004174.4	P2
SLC9A3-AS1	ENST00000607286.5	n.56C>G		non_coding_transcript_exon_variant	1/7	5
SLC9A3	ENST00000644203.1	c.2343G>C	p.Gln781His	missense_variant	16/16			A2

Frequencies

GnomAD3 genomes AF: 0.00319 AC: 482 AN: 151228 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.00450

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00763

Gnomad ASJ AF: 0.00953

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0261

Gnomad NFE AF: 0.00174

Gnomad OTH AF: 0.00966

GnomAD4 exome AF: 0.00164 AC: 1895 AN: 1157516 Hom.: 14 Cov.: 19 AF XY: 0.00167 AC XY: 947 AN XY: 566706

Gnomad4 AFR exome AF: 0.00517

Gnomad4 AMR exome AF: 0.00629

Gnomad4 ASJ exome AF: 0.0112

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000105

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00127

Gnomad4 OTH exome AF: 0.00467

GnomAD4 genome AF: 0.00319 AC: 483 AN: 151336 Hom.: 1 Cov.: 34 AF XY: 0.00335 AC XY: 248 AN XY: 73960

Gnomad4 AFR AF: 0.00452

Gnomad4 AMR AF: 0.00762

Gnomad4 ASJ AF: 0.00953

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00174

Gnomad4 OTH AF: 0.00956

Alfa AF: 0.000319 Hom.: 0

Bravo AF: 0.00402

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

SLC9A3: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	7.3
Dann	Benign	0.24
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.0058	T
GERP RS		0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs540024518; hg19: chr5-473406;