Genetic Variant NM_178527.4:c.3223C>G (chr1-173506858-G-C) – 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_178527.4(SLC9C2):c.3223C>G(p.Gln1075Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000121 in 1,611,108 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign 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 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

SLC9C2
NM_178527.4 missense, splice_region

Scores

Splicing: ADA: 0.1094

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.16

Publications

0 publications found

Variant links:

Genes affected

SLC9C2 (HGNC:28664): (solute carrier family 9 member C2 (putative)) Predicted to enable potassium:proton antiporter activity and sodium:proton antiporter activity. Predicted to be involved in potassium ion transmembrane transport; regulation of intracellular pH; and sodium ion import across plasma membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC9C2 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=0.041968346).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178527.4. 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
	SLC9C2	NM_178527.4	MANE Select	c.3223C>G	p.Gln1075Glu	missense splice_region	Exon 25 of 28	NP_848622.2	Q5TAH2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9C2	ENST00000367714.4	TSL:1 MANE Select	c.3223C>G	p.Gln1075Glu	missense splice_region	Exon 25 of 28	ENSP00000356687.3	Q5TAH2
	SLC9C2	ENST00000466087.1	TSL:1	n.2557C>G		splice_region non_coding_transcript_exon	Exon 18 of 21

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000245

AC:

AN:

248570

AF XY:

0.000216

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00430

Gnomad EAS exome

AF:

0.000383

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000533

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.000120

AC:

175

AN:

1458844

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

725700

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33302

American (AMR)

AF:

0.00

AC:

AN:

44308

Ashkenazi Jewish (ASJ)

AF:

0.00438

AC:

114

AN:

26046

East Asian (EAS)

AF:

0.000253

AC:

AN:

39574

South Asian (SAS)

AF:

0.0000466

AC:

AN:

85748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000270

AC:

AN:

1110526

Other (OTH)

AF:

0.000282

AC:

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

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:

0.000131

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41542

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00404

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68022

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.000273

Hom.:

Bravo

AF:

0.000204

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000206

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

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

0.089

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.68

M_CAP

Benign

0.0098

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

2.9

PhyloP100

5.2

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.2

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.56

MVP

0.62

MPC

0.89

ClinPred

0.23

GERP RS

4.8

Varity_R

0.53

gMVP

0.28

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.11

dbscSNV1_RF

Benign

0.34

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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