Genetic Variant NM_001384763.1:c.1035G>T (chr16-89196305-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001384763.1(SLC22A31):c.1035G>T(p.Arg345Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,459,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

SLC22A31
NM_001384763.1 missense, splice_region

Scores

Splicing: ADA: 0.5486

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.302

Variant links:

Genes affected

SLC22A31 (HGNC:27091): (solute carrier family 22 member 31) Predicted to enable transmembrane transporter activity. Predicted to be involved in ion transport and transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC22A31 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.904

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A31	NM_001384763.1 link	c.1035G>T	p.Arg345Ser	missense_variant, splice_region_variant	Exon 9 of 9	ENST00000682282.1	NP_001371692.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A31	ENST00000682282.1 link	c.1035G>T	p.Arg345Ser	missense_variant, splice_region_variant	Exon 9 of 9		NM_001384763.1	ENSP00000508250.1		A0A804HL90

Frequencies

GnomAD3 genomes

AF:

0.0000401

AC:

AN:

149746

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000290

Gnomad EAS

AF:

0.000200

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000595

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000140

AC:

AN:

71508

Hom.:

AF XY:

0.0000258

AC XY:

AN XY:

38782

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:

0.0000407

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000191

AC:

AN:

1309184

Hom.:

Cov.:

AF XY:

0.0000202

AC XY:

AN XY:

643864

show subpopulations

Gnomad4 AFR exome

AF:

0.0000682

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000941

Gnomad4 EAS exome

AF:

0.0000890

Gnomad4 SAS exome

AF:

0.0000142

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000125

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000400

AC:

AN:

149860

Hom.:

Cov.:

AF XY:

0.0000273

AC XY:

AN XY:

73188

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000290

Gnomad4 EAS

AF:

0.000201

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000595

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.711G>T (p.R237S) alteration is located in exon 8 (coding exon 6) of the SLC22A31 gene. This alteration results from a G to T substitution at nucleotide position 711, causing the arginine (R) at amino acid position 237 to be replaced by a serine (S). 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

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.48

CADD

Benign

DANN

Benign

0.62

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.062

MetaRNN

Pathogenic

0.90

D;D

PrimateAI

Uncertain

0.64

Sift4G

Pathogenic

0.0

D;D

Vest4

0.89

MVP

0.32

GERP RS

0.71

Varity_R

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.55

dbscSNV1_RF

Benign

0.52

SpliceAI score (max)

0.17

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