chr16-31483196-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003041.4(SLC5A2):ā€‹c.60T>Cā€‹(p.Ile20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,614,016 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0064 ( 17 hom., cov: 32)
Exomes š‘“: 0.00061 ( 7 hom. )

Consequence

SLC5A2
NM_003041.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0310
Variant links:
Genes affected
SLC5A2 (HGNC:11037): (solute carrier family 5 member 2) This gene encodes a member of the sodium glucose cotransporter family which are sodium-dependent glucose transport proteins. The encoded protein is the major cotransporter involved in glucose reabsorption in the kidney. Mutations in this gene are associated with renal glucosuria. Two transcript variants, one protein-coding and one not, have been found for this gene. [provided by RefSeq, Feb 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 16-31483196-T-C is Benign according to our data. Variant chr16-31483196-T-C is described in ClinVar as [Benign]. Clinvar id is 777013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.031 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0064 (974/152232) while in subpopulation AFR AF= 0.0225 (934/41540). AF 95% confidence interval is 0.0213. There are 17 homozygotes in gnomad4. There are 439 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 17 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC5A2NM_003041.4 linkuse as main transcriptc.60T>C p.Ile20= synonymous_variant 1/14 ENST00000330498.4
SLC5A2XM_006721072.5 linkuse as main transcriptc.60T>C p.Ile20= synonymous_variant 1/13
SLC5A2XM_024450402.2 linkuse as main transcriptc.60T>C p.Ile20= synonymous_variant 1/11
SLC5A2NR_130783.2 linkuse as main transcriptn.74T>C non_coding_transcript_exon_variant 1/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC5A2ENST00000330498.4 linkuse as main transcriptc.60T>C p.Ile20= synonymous_variant 1/141 NM_003041.4 P1P31639-1
SLC5A2ENST00000419665.6 linkuse as main transcriptc.60T>C p.Ile20= synonymous_variant, NMD_transcript_variant 1/121 P31639-2
SLC5A2ENST00000569576.5 linkuse as main transcriptc.-4+128T>C intron_variant 4
SLC5A2ENST00000562006.1 linkuse as main transcriptn.59T>C non_coding_transcript_exon_variant 1/33

Frequencies

GnomAD3 genomes
AF:
0.00640
AC:
973
AN:
152114
Hom.:
17
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0225
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00164
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00432
GnomAD3 exomes
AF:
0.00168
AC:
423
AN:
251380
Hom.:
5
AF XY:
0.00110
AC XY:
149
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.0234
Gnomad AMR exome
AF:
0.00104
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.000610
AC:
891
AN:
1461784
Hom.:
7
Cov.:
32
AF XY:
0.000481
AC XY:
350
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.0225
Gnomad4 AMR exome
AF:
0.00114
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:
0.00000899
Gnomad4 OTH exome
AF:
0.00124
GnomAD4 genome
AF:
0.00640
AC:
974
AN:
152232
Hom.:
17
Cov.:
32
AF XY:
0.00590
AC XY:
439
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.0225
Gnomad4 AMR
AF:
0.00157
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00427
Alfa
AF:
0.00334
Hom.:
1
Bravo
AF:
0.00696
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -
Familial renal glucosuria Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
CADD
Benign
0.51
DANN
Benign
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

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

Other links and lift over

dbSNP: rs114050461; hg19: chr16-31494517; API