15-34230149-TA-TAA

Variant names:

• chr15-34230149-T-TA
• rs566558212
• NM_001365088.1:c.*3731dupT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001365088.1(SLC12A6):​c.*3731dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 235,650 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: SLC12A6 NM_001365088.1 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.12
• Publications: 0 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]

EMC4 (HGNC:28032): (ER membrane protein complex subunit 4) Contributes to membrane insertase activity. Involved in protein insertion into ER membrane by stop-transfer membrane-anchor sequence and tail-anchored membrane protein insertion into ER membrane. Is integral component of endoplasmic reticulum membrane. Part of EMC complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.*3731dupT		3_prime_UTR	Exon 26 of 26	NP_001352017.1	Q9UHW9-1
	SLC12A6	NM_133647.2		c.*3731dupT		3_prime_UTR	Exon 25 of 25	NP_598408.1	Q9UHW9-1
	SLC12A6	NM_001042496.2		c.*3731dupT		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.*3731dupT		3_prime_UTR	Exon 26 of 26	ENSP00000346112.3	Q9UHW9-1
	SLC12A6	ENST00000290209.9	TSL:1	c.*3731dupT		3_prime_UTR	Exon 25 of 25	ENSP00000290209.5	Q9UHW9-2
	SLC12A6	ENST00000676379.1		c.*2350dupT		3_prime_UTR	Exon 26 of 26	ENSP00000502539.1	A0A6Q8PH21

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152134 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000661

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000120 AC: 10 AN: 83398 Hom.: 1 Cov.: 0 AF XY: 0.000141 AC XY: 6 AN XY: 42654

African (AFR) AF: 0.00 AC: 0 AN: 3058

American (AMR) AF: 0.00 AC: 0 AN: 2742

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3604

East Asian (EAS) AF: 0.00 AC: 0 AN: 6404

South Asian (SAS) AF: 0.00 AC: 0 AN: 2002

European-Finnish (FIN) AF: 0.000501 AC: 2 AN: 3996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 434

European-Non Finnish (NFE) AF: 0.000126 AC: 7 AN: 55402

Other (OTH) AF: 0.000174 AC: 1 AN: 5756

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152252 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74434

African (AFR) AF: 0.0000481 AC: 2 AN: 41560

American (AMR) AF: 0.000131 AC: 2 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000661 AC: 7 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000285 Hom.: 0

Bravo AF: 0.000219

ClinVar

ClinVar submissions

Significance: Uncertain significance

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
PhyloP100		-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: rs566558212; hg19: chr15-34522350;