5-128186851-C-A

Variant names:

• chr5-128186851-C-A
• rs10089
• NM_001046.3:c.*220C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001046.3(SLC12A2):​c.*220C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC12A2 NM_001046.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• Publications: 32 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.*220C>A		3_prime_UTR	Exon 27 of 27	NP_001037.1	Q53ZR1
	SLC12A2	NM_001256461.2		c.*220C>A		3_prime_UTR	Exon 26 of 26	NP_001243390.1	P55011-3
	SLC12A2	NR_046207.2		n.4114C>A		non_coding_transcript_exon	Exon 27 of 27

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A2	ENST00000262461.7	TSL:1 MANE Select	c.*220C>A		3_prime_UTR	Exon 27 of 27	ENSP00000262461.2	P55011-1
	SLC12A2	ENST00000343225.4	TSL:1	c.*220C>A		3_prime_UTR	Exon 26 of 26	ENSP00000340878.4	P55011-3
	SLC12A2	ENST00000509205.5	TSL:1	n.*472C>A		non_coding_transcript_exon	Exon 27 of 27	ENSP00000427109.1	G3XAL9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 250324 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 128594

African (AFR) AF: 0.00 AC: 0 AN: 7814

American (AMR) AF: 0.00 AC: 0 AN: 9908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8906

East Asian (EAS) AF: 0.00 AC: 0 AN: 22360

South Asian (SAS) AF: 0.00 AC: 0 AN: 7900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1192

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 157968

Other (OTH) AF: 0.00 AC: 0 AN: 15894

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 11880

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.76
PhyloP100		0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10089; hg19: chr5-127522543;