Genetic Variant SLC9C1:p.Tyr1021Asn (chr3-112169053-A-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_183061.3(SLC9C1):c.3061T>A(p.Tyr1021Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000111 in 1,438,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SLC9C1
NM_183061.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.96

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.831

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.3061T>A	p.Tyr1021Asn	missense	Exon 25 of 29	NP_898884.1	Q4G0N8-1
SLC9C1	NM_001320531.2		c.2917T>A	p.Tyr973Asn	missense	Exon 24 of 28	NP_001307460.1	Q4G0N8-2
SLC9C1	NR_135297.2		n.2331T>A		non_coding_transcript_exon	Exon 19 of 23

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC9C1	ENST00000305815.10	TSL:2 MANE Select	c.3061T>A	p.Tyr1021Asn	missense	Exon 25 of 29	ENSP00000306627.5	Q4G0N8-1
SLC9C1	ENST00000487372.5	TSL:1	c.2917T>A	p.Tyr973Asn	missense	Exon 24 of 28	ENSP00000420688.1	Q4G0N8-2
SLC9C1	ENST00000471295.1	TSL:5	n.*1390T>A		non_coding_transcript_exon	Exon 18 of 22	ENSP00000418371.1	F8WCJ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000176

AC:

AN:

227690

AF XY:

0.00000815

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000380

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1438640

Hom.:

Cov.:

AF XY:

0.00000840

AC XY:

AN XY:

714296

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32332

American (AMR)

AF:

0.0000249

AC:

AN:

40162

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24836

East Asian (EAS)

AF:

0.00

AC:

AN:

39488

South Asian (SAS)

AF:

0.00

AC:

AN:

80810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52244

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5654

European-Non Finnish (NFE)

AF:

0.0000136

AC:

AN:

1103730

Other (OTH)

AF:

0.00

AC:

AN:

59384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

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

0.27

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.079

MetaRNN

Pathogenic

0.83

MetaSVM

Uncertain

0.086

MutationAssessor

Uncertain

2.7

PhyloP100

5.0

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-6.6

REVEL

Uncertain

0.55

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.82

MutPred

0.50

Gain of disorder (P = 0.0376)

MVP

0.66

MPC

0.45

ClinPred

0.98

GERP RS

6.1

Varity_R

0.82

gMVP

0.41

Mutation Taster

=88/12

polymorphism

(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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over