rs4530104

Variant names:

• chr15-34230478-C-T
• rs4530104
• NM_001365088.1:c.*3403G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-34230478-C-T
• chr15-34230478-C-A
• chr15-34230478-C-G

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.*3403G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 152,376 control chromosomes in the GnomAD database, including 27,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (27663 hom., cov: 32)
  • Exomes 𝑓: 0.75 (100 hom.)
• Consequence: SLC12A6 NM_001365088.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0190
• Publications: 5 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=-0.7).
• BP6: Variant 15-34230478-C-T is Benign according to our data. Variant chr15-34230478-C-T is described in ClinVar as Benign. ClinVar VariationId is 315550.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 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.*3403G>A		3_prime_UTR	Exon 26 of 26	NP_001352017.1	Q9UHW9-1
	SLC12A6	NM_133647.2		c.*3403G>A		3_prime_UTR	Exon 25 of 25	NP_598408.1	Q9UHW9-1
	SLC12A6	NM_001042496.2		c.*3403G>A		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.*3403G>A		3_prime_UTR	Exon 26 of 26	ENSP00000346112.3	Q9UHW9-1
	SLC12A6	ENST00000290209.9	TSL:1	c.*3403G>A		3_prime_UTR	Exon 25 of 25	ENSP00000290209.5	Q9UHW9-2
	SLC12A6	ENST00000676379.1		c.*2022G>A		3_prime_UTR	Exon 26 of 26	ENSP00000502539.1	A0A6Q8PH21

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88850 AN: 151904 Hom.: 27660 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.618

GnomAD4 exome AF: 0.751 AC: 266 AN: 354 Hom.: 100 Cov.: 0 AF XY: 0.741 AC XY: 163 AN XY: 220

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 2 AN: 4

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.756 AC: 251 AN: 332

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.667 AC: 4 AN: 6

Other (OTH) AF: 0.800 AC: 8 AN: 10

GnomAD4 genome AF: 0.585 AC: 88885 AN: 152022 Hom.: 27663 Cov.: 32 AF XY: 0.590 AC XY: 43835 AN XY: 74302

African (AFR) AF: 0.344 AC: 14253 AN: 41414

American (AMR) AF: 0.679 AC: 10376 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2206 AN: 3470

East Asian (EAS) AF: 0.692 AC: 3578 AN: 5172

South Asian (SAS) AF: 0.601 AC: 2899 AN: 4824

European-Finnish (FIN) AF: 0.716 AC: 7555 AN: 10546

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46009 AN: 68008

Other (OTH) AF: 0.619 AC: 1306 AN: 2110

Alfa AF: 0.643 Hom.: 40759

Bravo AF: 0.572

Asia WGS AF: 0.641 AC: 2228 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	-0.70
CADD	Benign	6.8
DANN	Benign	0.73
PhyloP100		0.019

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: rs4530104; hg19: chr15-34522679;