Genetic Variant SLC9C1:p.Met1023Ile (chr3-112169045-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_183061.3(SLC9C1):c.3069G>T(p.Met1023Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,440,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLC9C1
NM_183061.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25156683).

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.3069G>T	p.Met1023Ile	missense	Exon 25 of 29	NP_898884.1	Q4G0N8-1
SLC9C1	NM_001320531.2		c.2925G>T	p.Met975Ile	missense	Exon 24 of 28	NP_001307460.1	Q4G0N8-2
SLC9C1	NR_135297.2		n.2339G>T		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.3069G>T	p.Met1023Ile	missense	Exon 25 of 29	ENSP00000306627.5	Q4G0N8-1
SLC9C1	ENST00000487372.5	TSL:1	c.2925G>T	p.Met975Ile	missense	Exon 24 of 28	ENSP00000420688.1	Q4G0N8-2
SLC9C1	ENST00000471295.1	TSL:5	n.*1398G>T		non_coding_transcript_exon	Exon 18 of 22	ENSP00000418371.1	F8WCJ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1440812

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715754

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32384

American (AMR)

AF:

0.00

AC:

AN:

40314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24906

East Asian (EAS)

AF:

0.00

AC:

AN:

39530

South Asian (SAS)

AF:

0.00

AC:

AN:

81068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5656

European-Non Finnish (NFE)

AF:

0.00000271

AC:

AN:

1105110

Other (OTH)

AF:

0.00

AC:

AN:

59446

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

Cov.:

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

0.32

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.069

Eigen

Benign

0.023

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.85

M_CAP

Benign

0.036

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.5

PhyloP100

2.7

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.1

REVEL

Benign

0.20

Sift

Benign

0.059

Sift4G

Uncertain

0.023

Polyphen

0.52

Vest4

0.37

MutPred

0.33

Gain of sheet (P = 0.0477)

MVP

0.52

MPC

0.14

ClinPred

0.65

GERP RS

5.2

Varity_R

0.27

gMVP

0.22

Mutation Taster

=86/14

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over