3-112155055-TAAAA-TAAAAAA

Variant names:

• chr3-112155055-T-TAA
• rs11369523
• NM_183061.3:c.3365-8_3365-7dupTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_183061.3(SLC9C1):​c.3365-8_3365-7dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,314,350 control chromosomes in the GnomAD database, including 68 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.012 (31 hom., cov: 0)
  • Exomes 𝑓: 0.14 (37 hom.)
• Consequence: SLC9C1 NM_183061.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.97
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.068 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9C1	NM_183061.3	MANE Select	c.3365-8_3365-7dupTT		splice_region intron	N/A	NP_898884.1	Q4G0N8-1
	SLC9C1	NM_001320531.2		c.3221-8_3221-7dupTT		splice_region intron	N/A	NP_001307460.1	Q4G0N8-2
	SLC9C1	NR_135297.2		n.2635-8_2635-7dupTT		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9C1	ENST00000305815.10	TSL:2 MANE Select	c.3365-7_3365-6insTT		splice_region intron	N/A	ENSP00000306627.5	Q4G0N8-1
	SLC9C1	ENST00000487372.5	TSL:1	c.3221-7_3221-6insTT		splice_region intron	N/A	ENSP00000420688.1	Q4G0N8-2
	SLC9C1	ENST00000471295.1	TSL:5	n.*1694-7_*1694-6insTT		splice_region intron	N/A	ENSP00000418371.1	F8WCJ0

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1704 AN: 145264 Hom.: 32 Cov.: 0

Gnomad AFR AF: 0.00511

Gnomad AMI AF: 0.00225

Gnomad AMR AF: 0.00600

Gnomad ASJ AF: 0.00413

Gnomad EAS AF: 0.0726

Gnomad SAS AF: 0.0744

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.0163

Gnomad NFE AF: 0.00832

Gnomad OTH AF: 0.00763

GnomAD2 exomes AF: 0.148 AC: 23706 AN: 160354 AF XY: 0.149

Gnomad AFR exome AF: 0.0903

Gnomad AMR exome AF: 0.180

Gnomad ASJ exome AF: 0.116

Gnomad EAS exome AF: 0.316

Gnomad FIN exome AF: 0.0983

Gnomad NFE exome AF: 0.118

Gnomad OTH exome AF: 0.143

GnomAD4 exome AF: 0.137 AC: 160063 AN: 1169030 Hom.: 37 Cov.: 30 AF XY: 0.139 AC XY: 80969 AN XY: 582562

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0938 AC: 2513 AN: 26780

American (AMR) AF: 0.176 AC: 5147 AN: 29268

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2339 AN: 21336

East Asian (EAS) AF: 0.315 AC: 9229 AN: 29272

South Asian (SAS) AF: 0.216 AC: 14340 AN: 66468

European-Finnish (FIN) AF: 0.103 AC: 3850 AN: 37504

Middle Eastern (MID) AF: 0.111 AC: 494 AN: 4452

European-Non Finnish (NFE) AF: 0.127 AC: 115304 AN: 905738

Other (OTH) AF: 0.142 AC: 6847 AN: 48212

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0117 AC: 1703 AN: 145320 Hom.: 31 Cov.: 0 AF XY: 0.0135 AC XY: 950 AN XY: 70406

African (AFR) AF: 0.00515 AC: 204 AN: 39586

American (AMR) AF: 0.00599 AC: 87 AN: 14514

Ashkenazi Jewish (ASJ) AF: 0.00413 AC: 14 AN: 3388

East Asian (EAS) AF: 0.0722 AC: 362 AN: 5014

South Asian (SAS) AF: 0.0745 AC: 342 AN: 4592

European-Finnish (FIN) AF: 0.0136 AC: 120 AN: 8828

Middle Eastern (MID) AF: 0.0179 AC: 5 AN: 280

European-Non Finnish (NFE) AF: 0.00832 AC: 551 AN: 66248

Other (OTH) AF: 0.00807 AC: 16 AN: 1982

Alfa AF: 0.00201 Hom.: 903

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-4.0
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11369523; hg19: chr3-111873902; COSMIC: COSV59894105;