3-112155055-TAAAA-TAAAAAAAAA

Variant names:

• chr3-112155055-T-TAAAAA
• rs11369523
• NM_183061.3:c.3365-11_3365-7dupTTTTT

Variant summary

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

The NM_183061.3(SLC9C1):​c.3365-11_3365-7dupTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000552 in 1,267,584 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 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000055 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC9C1 NM_183061.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.97
• Publications: 0 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: Very rare variant in population databases, with high coverage

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.3365-11_3365-7dupTTTTT		splice_region intron	N/A	NP_898884.1	Q4G0N8-1
	SLC9C1	NM_001320531.2		c.3221-11_3221-7dupTTTTT		splice_region intron	N/A	NP_001307460.1	Q4G0N8-2
	SLC9C1	NR_135297.2		n.2635-11_2635-7dupTTTTT		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_3365-6insTTTTT		splice_region intron	N/A	ENSP00000306627.5	Q4G0N8-1
	SLC9C1	ENST00000487372.5	TSL:1	c.3221-7_3221-6insTTTTT		splice_region intron	N/A	ENSP00000420688.1	Q4G0N8-2
	SLC9C1	ENST00000471295.1	TSL:5	n.*1694-7_*1694-6insTTTTT		splice_region intron	N/A	ENSP00000418371.1	F8WCJ0

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 145382 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000552 AC: 7 AN: 1267584 Hom.: 0 Cov.: 30 AF XY: 0.00000474 AC XY: 3 AN XY: 632788

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

African (AFR) AF: 0.0000351 AC: 1 AN: 28502

American (AMR) AF: 0.00 AC: 0 AN: 32442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22898

East Asian (EAS) AF: 0.00 AC: 0 AN: 35386

South Asian (SAS) AF: 0.00 AC: 0 AN: 72304

European-Finnish (FIN) AF: 0.0000493 AC: 2 AN: 40578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4758

European-Non Finnish (NFE) AF: 0.00000409 AC: 4 AN: 978074

Other (OTH) AF: 0.00 AC: 0 AN: 52642

⚠️ 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 145382 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 70412

African (AFR) AF: 0.00 AC: 0 AN: 39514

American (AMR) AF: 0.00 AC: 0 AN: 14512

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8846

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66308

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

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;