NM_183061.3:c.3365-9_3365-7dupTTT

Variant names:

• chr3-112155055-T-TAAA
• rs11369523
• NM_183061.3:c.3365-9_3365-7dupTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_183061.3(SLC9C1):​c.3365-9_3365-7dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,399,430 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000048 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0023 (0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Variant has high frequency in the SAS (0.00889) population. However there is too low homozygotes in high coverage region: (expected more than 1, got 0).

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.3365-9_3365-7dupTTT		splice_region intron	N/A	NP_898884.1	Q4G0N8-1
	SLC9C1	NM_001320531.2		c.3221-9_3221-7dupTTT		splice_region intron	N/A	NP_001307460.1	Q4G0N8-2
	SLC9C1	NR_135297.2		n.2635-9_2635-7dupTTT		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_3365-6insTTT		splice_region intron	N/A	ENSP00000306627.5	Q4G0N8-1
	SLC9C1	ENST00000487372.5	TSL:1	c.3221-7_3221-6insTTT		splice_region intron	N/A	ENSP00000420688.1	Q4G0N8-2
	SLC9C1	ENST00000471295.1	TSL:5	n.*1694-7_*1694-6insTTT		splice_region intron	N/A	ENSP00000418371.1	F8WCJ0

Frequencies

GnomAD3 genomes AF: 0.0000482 AC: 7 AN: 145358 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000433

Gnomad FIN AF: 0.000113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000302

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00370 AC: 594 AN: 160354 AF XY: 0.00345

Gnomad AFR exome AF: 0.00149

Gnomad AMR exome AF: 0.00488

Gnomad ASJ exome AF: 0.00252

Gnomad EAS exome AF: 0.0110

Gnomad FIN exome AF: 0.00192

Gnomad NFE exome AF: 0.00234

Gnomad OTH exome AF: 0.00491

GnomAD4 exome AF: 0.00226 AC: 2834 AN: 1254072 Hom.: 0 Cov.: 30 AF XY: 0.00244 AC XY: 1529 AN XY: 625808

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

African (AFR) AF: 0.00124 AC: 35 AN: 28280

American (AMR) AF: 0.00407 AC: 130 AN: 31918

Ashkenazi Jewish (ASJ) AF: 0.00168 AC: 38 AN: 22680

East Asian (EAS) AF: 0.00610 AC: 212 AN: 34744

South Asian (SAS) AF: 0.00948 AC: 671 AN: 70774

European-Finnish (FIN) AF: 0.00164 AC: 66 AN: 40238

Middle Eastern (MID) AF: 0.00190 AC: 9 AN: 4728

European-Non Finnish (NFE) AF: 0.00161 AC: 1555 AN: 968574

Other (OTH) AF: 0.00226 AC: 118 AN: 52136

⚠️ 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: 0.0000482 AC: 7 AN: 145358 Hom.: 0 Cov.: 0 AF XY: 0.0000568 AC XY: 4 AN XY: 70400

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

African (AFR) AF: 0.0000506 AC: 2 AN: 39510

American (AMR) AF: 0.00 AC: 0 AN: 14508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3390

East Asian (EAS) AF: 0.00 AC: 0 AN: 5034

South Asian (SAS) AF: 0.000433 AC: 2 AN: 4614

European-Finnish (FIN) AF: 0.000113 AC: 1 AN: 8838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000302 AC: 2 AN: 66300

Other (OTH) AF: 0.00 AC: 0 AN: 1970

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00353511), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 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;