rs5998330

Variant names:

• chr22-32238717-T-G
• rs5998330
• NM_014227.3:c.583+268A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014227.3(SLC5A4):​c.583+268A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,052 control chromosomes in the GnomAD database, including 15,738 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (15738 hom., cov: 31)
• Consequence: SLC5A4 NM_014227.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 5 publications found

Genes affected

SLC5A4 (HGNC:11039): (solute carrier family 5 member 4) Predicted to enable glucose:sodium symporter activity and proton transmembrane transporter activity. Predicted to be involved in sodium ion transport. Predicted to act upstream of or within proton transmembrane transport. Predicted to be active in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC5A4-AS1 (HGNC:53163): (SLC5A4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014227.3. 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
	SLC5A4	NM_014227.3	MANE Select	c.583+268A>C		intron	N/A	NP_055042.1
	SLC5A4-AS1	NR_149072.1		n.275-29571T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A4	ENST00000266086.6	TSL:1 MANE Select	c.583+268A>C		intron	N/A	ENSP00000266086.3
	SLC5A4-AS1	ENST00000434942.2	TSL:3	n.507+9345T>G		intron	N/A
	SLC5A4-AS1	ENST00000452181.2	TSL:5	n.275-29571T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67396 AN: 151934 Hom.: 15716 Cov.: 31

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.0611

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.444 AC: 67469 AN: 152052 Hom.: 15738 Cov.: 31 AF XY: 0.435 AC XY: 32310 AN XY: 74330

African (AFR) AF: 0.547 AC: 22666 AN: 41438

American (AMR) AF: 0.363 AC: 5545 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1539 AN: 3470

East Asian (EAS) AF: 0.0611 AC: 316 AN: 5174

South Asian (SAS) AF: 0.327 AC: 1577 AN: 4826

European-Finnish (FIN) AF: 0.376 AC: 3978 AN: 10580

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30411 AN: 67972

Other (OTH) AF: 0.403 AC: 852 AN: 2112

Alfa AF: 0.443 Hom.: 5853

Bravo AF: 0.445

Asia WGS AF: 0.253 AC: 884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.5
DANN	Benign	0.35
PhyloP100		0.058
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs5998330; hg19: chr22-32634704;