Genetic Variant NM_001384763.1:c.1196G>A (chr16-89196144-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001384763.1(SLC22A31):c.1196G>A(p.Arg399Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000821 in 1,534,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

SLC22A31
NM_001384763.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0800

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006955236).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384763.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC22A31	NM_001384763.1	MANE Select	c.1196G>A	p.Arg399Gln	missense	Exon 9 of 9	NP_001371692.1	A6NKX4-2
SLC22A31	NM_001366322.1		c.1142G>A	p.Arg381Gln	missense	Exon 9 of 9	NP_001353251.1
SLC22A31	NM_001384764.1		c.995G>A	p.Arg332Gln	missense	Exon 9 of 9	NP_001371693.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC22A31	ENST00000682282.1	MANE Select	c.1196G>A	p.Arg399Gln	missense	Exon 9 of 9	ENSP00000508250.1	A6NKX4-2
SLC22A31	ENST00000562855.7	TSL:5	c.872G>A	p.Arg291Gln	missense	Exon 9 of 9	ENSP00000474621.2	A0A087WY01
SLC22A31	ENST00000614943.4	TSL:5	c.872G>A	p.Arg291Gln	missense	Exon 8 of 8	ENSP00000481421.1	A0A087WY01

Frequencies

GnomAD3 genomes

AF:

0.000394

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000745

AC:

AN:

134264

AF XY:

0.0000684

show subpopulations

Gnomad AFR exome

AF:

0.00155

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000477

AC:

AN:

1382704

Hom.:

Cov.:

AF XY:

0.0000381

AC XY:

AN XY:

682298

show subpopulations

African (AFR)

AF:

0.00165

AC:

AN:

31558

American (AMR)

AF:

0.00

AC:

AN:

35678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25146

East Asian (EAS)

AF:

0.00

AC:

AN:

35722

South Asian (SAS)

AF:

0.00

AC:

AN:

79216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33664

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5390

European-Non Finnish (NFE)

AF:

0.00000742

AC:

AN:

1078500

Other (OTH)

AF:

0.000104

AC:

AN:

57830

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000394

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.00142

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.000778

Hom.:

Bravo

AF:

0.000468

ExAC

AF:

0.0000414

AC:

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

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.9

(source)

DANN

Benign

0.89

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.82

M_CAP

Benign

0.035

MetaRNN

Benign

0.0070

PhyloP100

0.080

PrimateAI

Uncertain

0.49

Sift4G

Benign

0.45

Vest4

0.034

MVP

0.21

GERP RS

-1.9

Varity_R

0.034

Mutation Taster

=97/3

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over