Variant 22-32218527-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014227.3(SLC5A4):c.1967G>A(p.Gly656Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,180 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC5A4
NM_014227.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.741

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A4	NM_014227.3 linkuse as main transcript	c.1967G>A	p.Gly656Asp	missense_variant	15/15	ENST00000266086.6
SLC5A4-AS1	NR_149072.1 linkuse as main transcript	n.274+11251C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLC5A4	ENST00000266086.6 linkuse as main transcript	c.1967G>A	p.Gly656Asp	missense_variant	15/15	1	NM_014227.3	P1
SLC5A4-AS1	ENST00000452181.2 linkuse as main transcript	n.274+11251C>T		intron_variant, non_coding_transcript_variant		5
SLC5A4-AS1	ENST00000434942.2 linkuse as main transcript	n.225-10563C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725602

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Feb 26, 2024

The c.1967G>A (p.G656D) alteration is located in exon 15 (coding exon 15) of the SLC5A4 gene. This alteration results from a G to A substitution at nucleotide position 1967, causing the glycine (G) at amino acid position 656 to be replaced by an aspartic acid (D). 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

Pathogenic

0.79

BayesDel_addAF

Uncertain

0.081

BayesDel_noAF

Benign

-0.12

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.32

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.33

M_CAP

Benign

0.0077

MetaRNN

Uncertain

0.72

MetaSVM

Uncertain

0.50

MutationAssessor

Pathogenic

3.4

MutationTaster

Benign

0.80

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-4.1

REVEL

Uncertain

0.47

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.013

Polyphen

0.95

Vest4

0.40

MutPred

0.73

Gain of disorder (P = 0.1408);

MVP

0.59

MPC

0.22

ClinPred

0.94

GERP RS

-1.2

Varity_R

0.46

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