3-112155055-TAAAA-TAAA

Variant names:

• chr3-112155055-TA-T
• rs11369523
• NM_183061.3:c.3365-7delT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_183061.3(SLC9C1):​c.3365-7delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00937 in 1,399,250 control chromosomes in the GnomAD database, including 3 homozygotes. 1/1 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: 𝑓 0.0035 (1 hom., cov: 0)
  • Exomes 𝑓: 0.010 (2 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.3365-7delT		splice_region intron	N/A	NP_898884.1	Q4G0N8-1
	SLC9C1	NM_001320531.2		c.3221-7delT		splice_region intron	N/A	NP_001307460.1	Q4G0N8-2
	SLC9C1	NR_135297.2		n.2635-7delT		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.3365-7delT		splice_region intron	N/A	ENSP00000306627.5	Q4G0N8-1
	SLC9C1	ENST00000487372.5	TSL:1	c.3221-7delT		splice_region intron	N/A	ENSP00000420688.1	Q4G0N8-2
	SLC9C1	ENST00000471295.1	TSL:5	n.*1694-7delT		splice_region intron	N/A	ENSP00000418371.1	F8WCJ0

Frequencies

GnomAD3 genomes AF: 0.00354 AC: 514 AN: 145364 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00108

Gnomad FIN AF: 0.00249

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00618

Gnomad OTH AF: 0.00305

GnomAD2 exomes AF: 0.0123 AC: 1980 AN: 160354 AF XY: 0.0121

Gnomad AFR exome AF: 0.0145

Gnomad AMR exome AF: 0.00709

Gnomad ASJ exome AF: 0.0139

Gnomad EAS exome AF: 0.00127

Gnomad FIN exome AF: 0.0156

Gnomad NFE exome AF: 0.0158

Gnomad OTH exome AF: 0.0116

GnomAD4 exome AF: 0.0100 AC: 12591 AN: 1253832 Hom.: 2 Cov.: 30 AF XY: 0.00983 AC XY: 6152 AN XY: 626088

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

African (AFR) AF: 0.00989 AC: 277 AN: 28000

American (AMR) AF: 0.00549 AC: 177 AN: 32212

Ashkenazi Jewish (ASJ) AF: 0.00830 AC: 187 AN: 22530

East Asian (EAS) AF: 0.000284 AC: 10 AN: 35270

South Asian (SAS) AF: 0.00466 AC: 335 AN: 71818

European-Finnish (FIN) AF: 0.00963 AC: 385 AN: 39990

Middle Eastern (MID) AF: 0.00445 AC: 21 AN: 4714

European-Non Finnish (NFE) AF: 0.0111 AC: 10764 AN: 967216

Other (OTH) AF: 0.00835 AC: 435 AN: 52082

⚠️ 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: 0.00353 AC: 514 AN: 145418 Hom.: 1 Cov.: 0 AF XY: 0.00309 AC XY: 218 AN XY: 70470

African (AFR) AF: 0.00136 AC: 54 AN: 39600

American (AMR) AF: 0.00124 AC: 18 AN: 14526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3388

East Asian (EAS) AF: 0.00 AC: 0 AN: 5020

South Asian (SAS) AF: 0.00109 AC: 5 AN: 4596

European-Finnish (FIN) AF: 0.00249 AC: 22 AN: 8842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.00617 AC: 409 AN: 66294

Other (OTH) AF: 0.00302 AC: 6 AN: 1986

Alfa AF: 0.00219 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

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs11369523; hg19: chr3-111873902;