dbSNP rs756267726: SLC9C1:p.Ala1146Thr (chr3-112151945-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_183061.3(SLC9C1):c.3436G>A(p.Ala1146Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000281 in 1,599,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

SLC9C1
NM_183061.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.470

Publications

2 publications found

Variant links:

Genes affected

SLC9C1 (HGNC:31401): (solute carrier family 9 member C1) 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 act upstream of or within flagellated sperm motility. Predicted to be located in motile cilium. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC9C1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06665489).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183061.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC9C1	NM_183061.3	MANE Select	c.3436G>A	p.Ala1146Thr	missense	Exon 28 of 29	NP_898884.1	Q4G0N8-1
SLC9C1	NM_001320531.2		c.3292G>A	p.Ala1098Thr	missense	Exon 27 of 28	NP_001307460.1	Q4G0N8-2
SLC9C1	NR_135297.2		n.2706G>A		non_coding_transcript_exon	Exon 22 of 23

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC9C1	ENST00000305815.10	TSL:2 MANE Select	c.3436G>A	p.Ala1146Thr	missense	Exon 28 of 29	ENSP00000306627.5	Q4G0N8-1
SLC9C1	ENST00000487372.5	TSL:1	c.3292G>A	p.Ala1098Thr	missense	Exon 27 of 28	ENSP00000420688.1	Q4G0N8-2
SLC9C1	ENST00000471295.1	TSL:5	n.*1765G>A		non_coding_transcript_exon	Exon 21 of 22	ENSP00000418371.1	F8WCJ0

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000211

AC:

AN:

236706

AF XY:

0.0000156

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000335

Gnomad ASJ exome

AF:

0.000107

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000274

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000283

AC:

AN:

1447688

Hom.:

Cov.:

AF XY:

0.0000361

AC XY:

AN XY:

720202

show subpopulations

African (AFR)

AF:

0.0000308

AC:

AN:

32422

American (AMR)

AF:

0.0000249

AC:

AN:

40138

Ashkenazi Jewish (ASJ)

AF:

0.0000392

AC:

AN:

25502

East Asian (EAS)

AF:

0.00

AC:

AN:

39358

South Asian (SAS)

AF:

0.00

AC:

AN:

83492

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53272

Middle Eastern (MID)

AF:

0.000180

AC:

AN:

5552

European-Non Finnish (NFE)

AF:

0.0000325

AC:

AN:

1108140

Other (OTH)

AF:

0.0000167

AC:

AN:

59812

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:

0.0000263

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41446

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:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000434

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000330

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

0.086

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.9

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.016

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.011

M_CAP

Benign

0.012

MetaRNN

Benign

0.067

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.20

PhyloP100

0.47

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.33

REVEL

Benign

0.071

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.052

Vest4

0.12

MVP

0.26

MPC

0.057

ClinPred

0.15

GERP RS

-0.75

Varity_R

0.096

gMVP

0.085

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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