rs62239058

Variant names:

• chr22-32247473-C-A
• rs62239058
• NM_014227.3:c.415G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-32247473-C-A
• chr22-32247473-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_014227.3(SLC5A4):​c.415G>T​(p.Glu139*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,613,390 control chromosomes in the GnomAD database, including 206 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. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.010 (8 hom., cov: 32)
  • Exomes 𝑓: 0.014 (198 hom.)
• Consequence: SLC5A4 NM_014227.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580
• Publications: 17 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0103 (1565/152288) while in subpopulation SAS AF = 0.0272 (131/4824). AF 95% confidence interval is 0.0234. There are 8 homozygotes in GnomAd4. There are 726 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

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.415G>T	p.Glu139*	stop_gained	Exon 5 of 15	NP_055042.1
	SLC5A4-AS1	NR_149072.1		n.275-20815C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A4	ENST00000266086.6	TSL:1 MANE Select	c.415G>T	p.Glu139*	stop_gained	Exon 5 of 15	ENSP00000266086.3
	SLC5A4-AS1	ENST00000434942.2	TSL:3	n.507+18101C>A		intron	N/A
	SLC5A4-AS1	ENST00000452181.2	TSL:5	n.275-20815C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1568 AN: 152170 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00244

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.00982

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0275

Gnomad FIN AF: 0.00443

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.0118 AC: 2975 AN: 251164 AF XY: 0.0128

Gnomad AFR exome AF: 0.00228

Gnomad AMR exome AF: 0.00831

Gnomad ASJ exome AF: 0.00417

Gnomad EAS exome AF: 0.00223

Gnomad FIN exome AF: 0.00444

Gnomad NFE exome AF: 0.0135

Gnomad OTH exome AF: 0.0126

GnomAD4 exome AF: 0.0137 AC: 20043 AN: 1461102 Hom.: 198 Cov.: 30 AF XY: 0.0142 AC XY: 10293 AN XY: 726896

African (AFR) AF: 0.00164 AC: 55 AN: 33462

American (AMR) AF: 0.00812 AC: 363 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00390 AC: 102 AN: 26130

East Asian (EAS) AF: 0.000957 AC: 38 AN: 39696

South Asian (SAS) AF: 0.0264 AC: 2278 AN: 86228

European-Finnish (FIN) AF: 0.00476 AC: 254 AN: 53402

Middle Eastern (MID) AF: 0.0139 AC: 80 AN: 5768

European-Non Finnish (NFE) AF: 0.0146 AC: 16174 AN: 1111354

Other (OTH) AF: 0.0116 AC: 699 AN: 60362

GnomAD4 genome AF: 0.0103 AC: 1565 AN: 152288 Hom.: 8 Cov.: 32 AF XY: 0.00975 AC XY: 726 AN XY: 74452

African (AFR) AF: 0.00243 AC: 101 AN: 41566

American (AMR) AF: 0.00980 AC: 150 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00577 AC: 20 AN: 3468

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5180

South Asian (SAS) AF: 0.0272 AC: 131 AN: 4824

European-Finnish (FIN) AF: 0.00443 AC: 47 AN: 10606

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0151 AC: 1024 AN: 68022

Other (OTH) AF: 0.0113 AC: 24 AN: 2116

Alfa AF: 0.0125 Hom.: 59

Bravo AF: 0.0101

TwinsUK AF: 0.0132 AC: 49

ALSPAC AF: 0.0132 AC: 51

ESP6500AA AF: 0.00272 AC: 12

ESP6500EA AF: 0.0149 AC: 128

ExAC AF: 0.0124 AC: 1506

Asia WGS AF: 0.0120 AC: 43 AN: 3478

EpiCase AF: 0.0159

EpiControl AF: 0.0157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	33
DANN	Uncertain	0.99
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.060	N
PhyloP100		-0.058
Vest4		0.19
GERP RS		0.57
Mutation Taster		=135/65	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.25		Position offset: 42
DS_DG_spliceai		0.22		Position offset: 6

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

Other links and lift over

dbSNP: rs62239058; hg19: chr22-32643460;