Genetic Variant NM_014227.3:c.1889C>G (chr22-32218605-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014227.3(SLC5A4):c.1889C>G(p.Thr630Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000132 in 151,976 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Consequence

SLC5A4
NM_014227.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.25

Publications

0 publications found

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:53163): (SLC5A4 antisense RNA 1)

SLC5A4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A4	NM_014227.3	MANE Select	c.1889C>G	p.Thr630Arg	missense	Exon 15 of 15	NP_055042.1	Q9NY91
	SLC5A4-AS1	NR_149072.1		n.274+11329G>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC5A4	ENST00000266086.6	TSL:1 MANE Select	c.1889C>G	p.Thr630Arg	missense	Exon 15 of 15	ENSP00000266086.3	Q9NY91
SLC5A4-AS1	ENST00000434942.2	TSL:3	n.225-10485G>C		intron	N/A
SLC5A4-AS1	ENST00000452181.2	TSL:5	n.274+11329G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151976

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41354

American (AMR)

AF:

0.000131

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.13

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.53

MetaSVM

Uncertain

0.14

MutationAssessor

Pathogenic

3.1

PhyloP100

4.2

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.53

Sift

Benign

0.098

Sift4G

Uncertain

0.060

Polyphen

0.60

Vest4

0.62

MutPred

0.28

Gain of MoRF binding (P = 0.0226)

MVP

0.55

MPC

0.70

ClinPred

0.76

GERP RS

3.2

Varity_R

0.22

gMVP

0.57

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over