15-34230784-C-G

Variant names:

• chr15-34230784-C-G
• rs4238571
• NM_001365088.1:c.*3097G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001365088.1(SLC12A6):​c.*3097G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.968 in 152,750 control chromosomes in the GnomAD database, including 71,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.97 (71524 hom., cov: 32)
  • Exomes 𝑓: 1.0 (218 hom.)
• Consequence: SLC12A6 NM_001365088.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.176
• Publications: 3 publications found

Genes affected

SLC12A6 (HGNC:10914): (solute carrier family 12 member 6) This gene is a member of the K-Cl cotransporter (KCC) family. K-Cl cotransporters are integral membrane proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The proteins encoded by this gene are activated by cell swelling induced by hypotonic conditions. Alternate splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are associated with agenesis of the corpus callosum with peripheral neuropathy. [provided by RefSeq, Jul 2008]

SLC12A6 Gene-Disease associations (from GenCC):

• agenesis of the corpus callosum with peripheral neuropathy

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics, Orphanet
• Charcot-Marie-Tooth disease, axonal, IIa 2II

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 15-34230784-C-G is Benign according to our data. Variant chr15-34230784-C-G is described in ClinVar as Benign. ClinVar VariationId is 315556.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365088.1. 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
	SLC12A6	NM_001365088.1	MANE Select	c.*3097G>C		3_prime_UTR	Exon 26 of 26	NP_001352017.1	Q9UHW9-1
	SLC12A6	NM_133647.2		c.*3097G>C		3_prime_UTR	Exon 25 of 25	NP_598408.1	Q9UHW9-1
	SLC12A6	NM_001042496.2		c.*3097G>C		3_prime_UTR	Exon 26 of 26	NP_001035961.1	Q9UHW9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A6	ENST00000354181.8	TSL:1 MANE Select	c.*3097G>C		3_prime_UTR	Exon 26 of 26	ENSP00000346112.3	Q9UHW9-1
	SLC12A6	ENST00000290209.9	TSL:1	c.*3097G>C		3_prime_UTR	Exon 25 of 25	ENSP00000290209.5	Q9UHW9-2
	SLC12A6	ENST00000676379.1		c.*1716G>C		3_prime_UTR	Exon 26 of 26	ENSP00000502539.1	A0A6Q8PH21

Frequencies

GnomAD3 genomes AF: 0.968 AC: 147335 AN: 152196 Hom.: 71490 Cov.: 32

Gnomad AFR AF: 0.891

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.986

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.972

GnomAD4 exome AF: 1.00 AC: 436 AN: 436 Hom.: 218 Cov.: 0 AF XY: 1.00 AC XY: 264 AN XY: 264

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 426 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 4 AN: 4

Other (OTH) AF: 1.00 AC: 6 AN: 6

GnomAD4 genome AF: 0.968 AC: 147424 AN: 152314 Hom.: 71524 Cov.: 32 AF XY: 0.970 AC XY: 72260 AN XY: 74486

African (AFR) AF: 0.890 AC: 36970 AN: 41522

American (AMR) AF: 0.986 AC: 15094 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3463 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5192 AN: 5192

South Asian (SAS) AF: 0.999 AC: 4829 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10620 AN: 10620

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67996 AN: 68048

Other (OTH) AF: 0.973 AC: 2056 AN: 2114

Alfa AF: 0.993 Hom.: 3494

Bravo AF: 0.964

Asia WGS AF: 0.993 AC: 3453 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Agenesis of the corpus callosum with peripheral neuropathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.2
DANN	Benign	0.66
PhyloP100		0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs4238571; hg19: chr15-34522985;