5-1052245-C-T

Variant names:

• chr5-1052245-C-T
• rs3810854
• NM_006598.3:c.*115G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006598.3(SLC12A7):​c.*115G>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 0.519 in 870,066 control chromosomes in the GnomAD database, including 118,094 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (21538 hom., cov: 33)
  • Exomes 𝑓: 0.52 (96556 hom.)
• Consequence: SLC12A7 NM_006598.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.73
• Publications: 24 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.009).
• BP6: Variant 5-1052245-C-T is Benign according to our data. Variant chr5-1052245-C-T is described in ClinVar as Benign. ClinVar VariationId is 1270319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 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.*115G>A		3_prime_UTR	Exon 24 of 24	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.*115G>A		3_prime_UTR	Exon 24 of 24	ENSP00000264930.5	Q9Y666-1
	SLC12A7	ENST00000634447.1	TSL:5	c.*115G>A		3_prime_UTR	Exon 23 of 23	ENSP00000489285.1	A0A0U1RR18
	SLC12A7	ENST00000945163.1		c.*115G>A		3_prime_UTR	Exon 26 of 26	ENSP00000615222.1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80664 AN: 151938 Hom.: 21504 Cov.: 33

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.559

GnomAD2 exomes AF: 0.527 AC: 112037 AN: 212554 AF XY: 0.523

Gnomad AFR exome AF: 0.559

Gnomad AMR exome AF: 0.547

Gnomad ASJ exome AF: 0.600

Gnomad EAS exome AF: 0.620

Gnomad FIN exome AF: 0.519

Gnomad NFE exome AF: 0.500

Gnomad OTH exome AF: 0.526

GnomAD4 exome AF: 0.516 AC: 370822 AN: 718010 Hom.: 96556 Cov.: 9 AF XY: 0.515 AC XY: 196266 AN XY: 381438

African (AFR) AF: 0.559 AC: 10761 AN: 19252

American (AMR) AF: 0.551 AC: 21871 AN: 39722

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 12083 AN: 19960

East Asian (EAS) AF: 0.650 AC: 23480 AN: 36102

South Asian (SAS) AF: 0.516 AC: 34901 AN: 67652

European-Finnish (FIN) AF: 0.516 AC: 22513 AN: 43662

Middle Eastern (MID) AF: 0.578 AC: 2420 AN: 4188

European-Non Finnish (NFE) AF: 0.496 AC: 223986 AN: 451876

Other (OTH) AF: 0.528 AC: 18807 AN: 35596

GnomAD4 genome AF: 0.531 AC: 80750 AN: 152056 Hom.: 21538 Cov.: 33 AF XY: 0.535 AC XY: 39794 AN XY: 74328

African (AFR) AF: 0.554 AC: 22976 AN: 41504

American (AMR) AF: 0.568 AC: 8680 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2078 AN: 3470

East Asian (EAS) AF: 0.615 AC: 3147 AN: 5116

South Asian (SAS) AF: 0.519 AC: 2501 AN: 4818

European-Finnish (FIN) AF: 0.519 AC: 5503 AN: 10594

Middle Eastern (MID) AF: 0.603 AC: 176 AN: 292

European-Non Finnish (NFE) AF: 0.499 AC: 33889 AN: 67954

Other (OTH) AF: 0.562 AC: 1185 AN: 2108

Alfa AF: 0.512 Hom.: 50069

Bravo AF: 0.537

Asia WGS AF: 0.602 AC: 2096 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.51
PhyloP100		-2.7
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: rs3810854; hg19: chr5-1052360;