5-128137438-T-C

Variant names:

• chr5-128137438-T-C
• rs10519973
• NM_001046.3:c.1409-1159T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001046.3(SLC12A2):​c.1409-1159T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,208 control chromosomes in the GnomAD database, including 1,129 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (1129 hom., cov: 32)
• Consequence: SLC12A2 NM_001046.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 3 publications found

Genes affected

SLC12A2 (HGNC:10911): (solute carrier family 12 member 2) The protein encoded by this gene mediates sodium and chloride transport and reabsorption. The encoded protein is a membrane protein and is important in maintaining proper ionic balance and cell volume. This protein is phosphorylated in response to DNA damage. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

SLC12A2 Gene-Disease associations (from GenCC):

• Delpire-McNeill syndrome

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal dominant 78

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Kilquist syndrome

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001046.3. 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
	SLC12A2	NM_001046.3	MANE Select	c.1409-1159T>C		intron	N/A	NP_001037.1	Q53ZR1
	SLC12A2	NM_001256461.2		c.1409-1159T>C		intron	N/A	NP_001243390.1	P55011-3
	SLC12A2	NR_046207.2		n.1598-1159T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A2	ENST00000262461.7	TSL:1 MANE Select	c.1409-1159T>C		intron	N/A	ENSP00000262461.2	P55011-1
	SLC12A2	ENST00000343225.4	TSL:1	c.1409-1159T>C		intron	N/A	ENSP00000340878.4	P55011-3
	SLC12A2	ENST00000509205.5	TSL:1	n.1409-1159T>C		intron	N/A	ENSP00000427109.1	G3XAL9

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15329 AN: 152090 Hom.: 1123 Cov.: 32

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.105

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.101 AC: 15339 AN: 152208 Hom.: 1129 Cov.: 32 AF XY: 0.106 AC XY: 7883 AN XY: 74406

African (AFR) AF: 0.0241 AC: 1003 AN: 41574

American (AMR) AF: 0.214 AC: 3259 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3472

East Asian (EAS) AF: 0.250 AC: 1294 AN: 5168

South Asian (SAS) AF: 0.157 AC: 754 AN: 4814

European-Finnish (FIN) AF: 0.105 AC: 1110 AN: 10606

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7070 AN: 67998

Other (OTH) AF: 0.106 AC: 224 AN: 2110

Alfa AF: 0.105 Hom.: 493

Bravo AF: 0.107

Asia WGS AF: 0.200 AC: 696 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	15
DANN	Benign	0.75
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs10519973; hg19: chr5-127473130;