20-46021798-C-T

Variant names:

• chr20-46021798-C-T
• rs1285595400
• NM_001134771.2:c.33C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS1

The NM_001134771.2(SLC12A5):​c.33C>T​(p.Pro11Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000521 in 1,381,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000052 (0 hom.)
• Consequence: SLC12A5 NM_001134771.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.798
• Publications: 0 publications found

Genes affected

SLC12A5 (HGNC:13818): (solute carrier family 12 member 5) K-Cl cotransporters are proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The protein encoded by this gene is an integral membrane K-Cl cotransporter that can function in either a net efflux or influx pathway, depending on the chemical concentration gradients of potassium and chloride. The encoded protein can act as a homomultimer, or as a heteromultimer with other K-Cl cotransporters, to maintain chloride homeostasis in neurons. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Sep 2008]

SLC12A5-AS1 (HGNC:53143): (SLC12A5 and MMP9 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 20-46021798-C-T is Benign according to our data. Variant chr20-46021798-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3389112.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.798 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0000521 (72/1381086) while in subpopulation NFE AF = 0.0000668 (72/1078006). AF 95% confidence interval is 0.0000541. There are 0 homozygotes in GnomAdExome4. There are 31 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134771.2. 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
	SLC12A5	NM_001134771.2		c.33C>T	p.Pro11Pro	synonymous	Exon 1 of 26	NP_001128243.1	Q9H2X9-1
	SLC12A5-AS1	NR_147699.1		n.276G>A		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A5	ENST00000454036.6	TSL:5	c.33C>T	p.Pro11Pro	synonymous	Exon 1 of 26	ENSP00000387694.1	Q9H2X9-1
	SLC12A5	ENST00000626701.1	TSL:3	c.33C>T	p.Pro11Pro	synonymous	Exon 1 of 3	ENSP00000487372.1	A0A0D9SGD0
	SLC12A5	ENST00000628272.1	TSL:3	c.33C>T	p.Pro11Pro	synonymous	Exon 1 of 2	ENSP00000486382.1	A0A0D9SF89

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000155 AC: 2 AN: 128718 AF XY: 0.0000141

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000414

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000521 AC: 72 AN: 1381086 Hom.: 0 Cov.: 32 AF XY: 0.0000455 AC XY: 31 AN XY: 681688

African (AFR) AF: 0.00 AC: 0 AN: 31164

American (AMR) AF: 0.00 AC: 0 AN: 35630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25062

East Asian (EAS) AF: 0.00 AC: 0 AN: 35522

South Asian (SAS) AF: 0.00 AC: 0 AN: 79078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4538

European-Non Finnish (NFE) AF: 0.0000668 AC: 72 AN: 1078006

Other (OTH) AF: 0.00 AC: 0 AN: 57688

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Benign	0.97
PhyloP100		0.80
PromoterAI		-0.0050	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1285595400; hg19: chr20-44650437;