rs80090801

Variant names:

• chr5-1053637-A-G
• rs80090801
• NM_006598.3:c.3027-155T>C

Variant summary

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

The NM_006598.3(SLC12A7):​c.3027-155T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,232 control chromosomes in the GnomAD database, including 1,797 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (1797 hom., cov: 34)
• Consequence: SLC12A7 NM_006598.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0330
• Publications: 0 publications found

Genes affected

SLC12A7 (HGNC:10915): (solute carrier family 12 member 7) Enables protein kinase binding activity. Predicted to be involved in several processes, including cell volume homeostasis; inorganic ion homeostasis; and inorganic ion transmembrane transport. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

SLC12A7 Gene-Disease associations (from GenCC):

• renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-1053637-A-G is Benign according to our data. Variant chr5-1053637-A-G is described in ClinVar as Benign. ClinVar VariationId is 1235255.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006598.3. 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
	SLC12A7	NM_006598.3	MANE Select	c.3027-155T>C		intron	N/A	NP_006589.2	Q9Y666-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A7	ENST00000264930.10	TSL:1 MANE Select	c.3027-155T>C		intron	N/A	ENSP00000264930.5	Q9Y666-1
	SLC12A7	ENST00000634447.1	TSL:5	c.2742-155T>C		intron	N/A	ENSP00000489285.1	A0A0U1RR18
	SLC12A7	ENST00000945163.1		c.3144-155T>C		intron	N/A	ENSP00000615222.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15657 AN: 152114 Hom.: 1788 Cov.: 34

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0980

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.0309

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0160

Gnomad OTH AF: 0.0802

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.103 AC: 15703 AN: 152232 Hom.: 1797 Cov.: 34 AF XY: 0.103 AC XY: 7666 AN XY: 74464

African (AFR) AF: 0.278 AC: 11523 AN: 41516

American (AMR) AF: 0.0982 AC: 1502 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0588 AC: 204 AN: 3472

East Asian (EAS) AF: 0.130 AC: 673 AN: 5174

South Asian (SAS) AF: 0.0391 AC: 189 AN: 4828

European-Finnish (FIN) AF: 0.0309 AC: 328 AN: 10612

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0160 AC: 1085 AN: 68018

Other (OTH) AF: 0.0799 AC: 169 AN: 2116

Alfa AF: 0.0775 Hom.: 155

Bravo AF: 0.118

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.90
CADD	Benign	2.0
DANN	Benign	0.37
PhyloP100		0.033
Mutation Taster		=100/0	polymorphism (auto)

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: rs80090801; hg19: chr5-1053752;