Genetic Variant SLC9A8:c.1638+26T>C (chr20-49886924-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015266.3(SLC9A8):c.1638+26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0774 in 1,602,330 control chromosomes in the GnomAD database, including 5,293 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.098 ( 897 hom., cov: 32)

Exomes 𝑓: 0.075 ( 4396 hom. )

Consequence

SLC9A8
NM_015266.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.154

Publications

5 publications found

Variant links:

Genes affected

SLC9A8 (HGNC:20728): (solute carrier family 9 member A8) Sodium-hydrogen exchangers (NHEs), such as SLC9A8, are integral transmembrane proteins that exchange extracellular Na+ for intracellular H+. NHEs have multiple functions, including intracellular pH homeostasis, cell volume regulation, and electroneutral NaCl absorption in epithelia (Xu et al., 2008 [PubMed 18209477]).[supplied by OMIM, Apr 2009]

SLC9A8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015266.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC9A8	NM_015266.3	MANE Select	c.1638+26T>C	intron	N/A	NP_056081.1	Q9Y2E8-1
SLC9A8	NM_001260491.2		c.1686+26T>C	intron	N/A	NP_001247420.1	Q9Y2E8-2
SLC9A8	NR_048537.2		n.1698+26T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC9A8	ENST00000361573.3	TSL:1 MANE Select	c.1638+26T>C	intron	N/A	ENSP00000354966.2	Q9Y2E8-1
SLC9A8	ENST00000851371.1		c.1737+26T>C	intron	N/A	ENSP00000521430.1
SLC9A8	ENST00000417961.5	TSL:2	c.1686+26T>C	intron	N/A	ENSP00000416418.1	Q9Y2E8-2

Frequencies

GnomAD3 genomes

AF:

0.0977

AC:

14854

AN:

152074

Hom.:

890

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.0923

Gnomad AMR

AF:

0.0668

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.0403

Gnomad SAS

AF:

0.0799

Gnomad FIN

AF:

0.0759

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0729

Gnomad OTH

AF:

0.102

GnomAD2 exomes

AF:

0.0816

AC:

19824

AN:

242978

AF XY:

0.0803

show subpopulations

Gnomad AFR exome

AF:

0.162

Gnomad AMR exome

AF:

0.0738

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.0373

Gnomad FIN exome

AF:

0.0753

Gnomad NFE exome

AF:

0.0751

Gnomad OTH exome

AF:

0.0841

GnomAD4 exome

AF:

0.0753

AC:

109150

AN:

1450138

Hom.:

4396

Cov.:

AF XY:

0.0757

AC XY:

54507

AN XY:

719996

show subpopulations

African (AFR)

AF:

0.166

AC:

5521

AN:

33292

American (AMR)

AF:

0.0744

AC:

3273

AN:

44006

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

3496

AN:

25462

East Asian (EAS)

AF:

0.0413

AC:

1624

AN:

39338

South Asian (SAS)

AF:

0.0822

AC:

6981

AN:

84914

European-Finnish (FIN)

AF:

0.0755

AC:

4000

AN:

53000

Middle Eastern (MID)

AF:

0.109

AC:

624

AN:

5718

European-Non Finnish (NFE)

AF:

0.0716

AC:

79033

AN:

1104554

Other (OTH)

AF:

0.0768

AC:

4598

AN:

59854

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

4913

9826

14739

19652

24565

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2970

5940

8910

11880

14850

<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:

0.0979

AC:

14902

AN:

152192

Hom.:

897

Cov.:

AF XY:

0.0959

AC XY:

7137

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.162

AC:

6703

AN:

41494

American (AMR)

AF:

0.0666

AC:

1019

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

487

AN:

3466

East Asian (EAS)

AF:

0.0401

AC:

207

AN:

5168

South Asian (SAS)

AF:

0.0804

AC:

388

AN:

4826

European-Finnish (FIN)

AF:

0.0759

AC:

805

AN:

10612

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0730

AC:

4962

AN:

68014

Other (OTH)

AF:

0.101

AC:

214

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

658

1316

1974

2632

3290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<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:

0.0945

Hom.:

162

Bravo

AF:

0.101

Asia WGS

AF:

0.0630

AC:

217

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.9

(source)

DANN

Benign

0.41

PhyloP100

-0.15

Mutation Taster

=100/0

polymorphism (auto)

(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

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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