Variant rs62239058 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP5BS1_SupportingBS2

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. Variant has been reported in Lovd as Pathogenic (no stars). 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0580

Variant links:

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 links:

SLC5A4-AS1 (HGNC:):

SLC5A4-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PP5

Variant 22-32247473-C-A is Pathogenic according to our data. Variant chr22-32247473-C-A is described in Lovd as [Pathogenic].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A4	NM_014227.3 linkuse as main transcript	c.415G>T	p.Glu139*	stop_gained	5/15	ENST00000266086.6	NP_055042.1	Q9NY91

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC5A4	ENST00000266086.6 linkuse as main transcript	c.415G>T	p.Glu139*	stop_gained	5/15	1	NM_014227.3	ENSP00000266086.3	Q9NY91
SLC5A4-AS1	ENST00000434942.2 linkuse as main transcript	n.507+18101C>A		intron_variant		3
SLC5A4-AS1	ENST00000452181.2 linkuse as main transcript	n.275-20815C>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1568

AN:

152170

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0118

AC:

2975

AN:

251164

Hom.:

AF XY:

0.0128

AC XY:

1736

AN XY:

135760

show subpopulations

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 SAS exome

AF:

0.0280

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.:

AF XY:

0.0142

AC XY:

10293

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.00812

Gnomad4 ASJ exome

AF:

0.00390

Gnomad4 EAS exome

AF:

0.000957

Gnomad4 SAS exome

AF:

0.0264

Gnomad4 FIN exome

AF:

0.00476

Gnomad4 NFE exome

AF:

0.0146

Gnomad4 OTH exome

AF:

0.0116

GnomAD4 genome

AF:

0.0103

AC:

1565

AN:

152288

Hom.:

Cov.:

AF XY:

0.00975

AC XY:

726

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00243

Gnomad4 AMR

AF:

0.00980

Gnomad4 ASJ

AF:

0.00577

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0272

Gnomad4 FIN

AF:

0.00443

Gnomad4 NFE

AF:

0.0151

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.0123

Hom.:

Bravo

AF:

0.0101

TwinsUK

AF:

0.0132

AC:

ALSPAC

AF:

0.0132

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.0149

AC:

128

ExAC

AF:

0.0124

AC:

1506

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0159

EpiControl

AF:

0.0157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.060

Vest4

0.19

GERP RS

0.57

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over