dbSNP rs755164607: SLC9C1:p.Ile1121Arg (chr3-112167223-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_183061.3(SLC9C1):c.3362T>G(p.Ile1121Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC9C1
NM_183061.3 missense, splice_region

Scores

Splicing: ADA: 0.00003706

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.61

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05188054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9C1	NM_183061.3 link	c.3362T>G	p.Ile1121Arg	missense_variant, splice_region_variant	Exon 26 of 29	ENST00000305815.10	NP_898884.1	Q4G0N8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC9C1	ENST00000305815.10 link	c.3362T>G	p.Ile1121Arg	missense_variant, splice_region_variant	Exon 26 of 29	2	NM_183061.3	ENSP00000306627.5	Q4G0N8-1
SLC9C1	ENST00000487372.5 link	c.3218T>G	p.Ile1073Arg	missense_variant, splice_region_variant	Exon 25 of 28	1		ENSP00000420688.1	Q4G0N8-2
SLC9C1	ENST00000471295.1 link	n.*1691T>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 19 of 22	5		ENSP00000418371.1	F8WCJ0
SLC9C1	ENST00000471295.1 link	n.*1691T>G		3_prime_UTR_variant	Exon 19 of 22	5		ENSP00000418371.1	F8WCJ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454774

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723584

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.011

DANN

Benign

0.35

DEOGEN2

Benign

0.021

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.013

M_CAP

Benign

0.034

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.34

N;.

PrimateAI

Benign

0.27

PROVEAN

Benign

0.56

N;N

REVEL

Benign

0.11

Sift

Benign

0.73

T;T

Sift4G

Benign

0.36

T;T

Polyphen

0.0

B;B

Vest4

0.24

MutPred

0.31

Gain of disorder (P = 0.0113);.;

MVP

0.13

MPC

0.094

ClinPred

0.030

GERP RS

-7.5

Varity_R

0.043

gMVP

0.064

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000037

dbscSNV1_RF

Benign

0.012

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over