21-34096385-A-C

Position:

chr21-34096385-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006933.7(SLC5A3):c.1187A>C(p.Lys396Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

SLC5A3
NM_006933.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.48

Variant links:

Genes affected

SLC5A3 (HGNC:11038): (solute carrier family 5 member 3) Enables potassium channel regulator activity and transmembrane transporter binding activity. Predicted to be involved in inositol metabolic process; monosaccharide transmembrane transport; and myo-inositol import across plasma membrane. Predicted to act upstream of or within several processes, including peripheral nervous system development; positive regulation of reactive oxygen species biosynthetic process; and regulation of respiratory gaseous exchange. Located in plasma membrane. Part of perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SLC5A3 links:

MRPS6 (HGNC:14051): (mitochondrial ribosomal protein S6) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein that belongs to the ribosomal protein S6P family. Pseudogenes corresponding to this gene are found on chromosomes 1p and 12q. [provided by RefSeq, Jul 2008]

MRPS6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20778525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A3	NM_006933.7 linkuse as main transcript	c.1187A>C	p.Lys396Thr	missense_variant	2/2	ENST00000381151.5	NP_008864.4
MRPS6	NM_032476.4 linkuse as main transcript	c.45+22640A>C		intron_variant		ENST00000399312.3	NP_115865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SLC5A3	ENST00000381151.5 linkuse as main transcript	c.1187A>C	p.Lys396Thr	missense_variant	2/2	1	NM_006933.7	ENSP00000370543	P1
MRPS6	ENST00000399312.3 linkuse as main transcript	c.45+22640A>C		intron_variant		1	NM_032476.4	ENSP00000382250	P1
MRPS6	ENST00000477091.5 linkuse as main transcript	n.198-6450A>C		intron_variant, non_coding_transcript_variant		5
MRPS6	ENST00000488492.5 linkuse as main transcript	n.46-6450A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000107

AC:

AN:

251168

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000238

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000123

AC:

180

AN:

1461854

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000156

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000812

Hom.:

Bravo

AF:

0.0000869

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.1187A>C (p.K396T) alteration is located in exon 2 (coding exon 1) of the SLC5A3 gene. This alteration results from a A to C substitution at nucleotide position 1187, causing the lysine (K) at amino acid position 396 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

0.019

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.94

M_CAP

Benign

0.058

MetaRNN

Benign

0.21

MetaSVM

Uncertain

-0.19

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.58

Sift

Benign

0.87

Sift4G

Benign

0.87

Vest4

0.42

MVP

0.19

MPC

0.72

ClinPred

0.13

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over