Genetic Variant SLC12A7:c.*115G>A (chr5-1052245-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.73

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 5-1052245-C-T is Benign according to our data. Variant chr5-1052245-C-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A7	NM_006598.3 link	c.*115G>A		3_prime_UTR_variant	Exon 24 of 24	ENST00000264930.10	NP_006589.2	Q9Y666-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A7	ENST00000264930 link	c.*115G>A		3_prime_UTR_variant	Exon 24 of 24	1	NM_006598.3	ENSP00000264930.5		Q9Y666-1
SLC12A7	ENST00000634447 link	c.*115G>A		3_prime_UTR_variant	Exon 23 of 23	5		ENSP00000489285.1		A0A0U1RR18

Frequencies

GnomAD3 genomes

AF:

0.531

AC:

80664

AN:

151938

Hom.:

21504

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.527

AC:

112037

AN:

212554

Hom.:

29460

AF XY:

0.523

AC XY:

60897

AN XY:

116352

show subpopulations

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 SAS exome

AF:

0.511

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.:

AF XY:

0.515

AC XY:

196266

AN XY:

381438

show subpopulations

Gnomad4 AFR exome

AF:

0.559

Gnomad4 AMR exome

AF:

0.551

Gnomad4 ASJ exome

AF:

0.605

Gnomad4 EAS exome

AF:

0.650

Gnomad4 SAS exome

AF:

0.516

Gnomad4 FIN exome

AF:

0.516

Gnomad4 NFE exome

AF:

0.496

Gnomad4 OTH exome

AF:

0.528

GnomAD4 genome

AF:

0.531

AC:

80750

AN:

152056

Hom.:

21538

Cov.:

AF XY:

0.535

AC XY:

39794

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.554

Gnomad4 AMR

AF:

0.568

Gnomad4 ASJ

AF:

0.599

Gnomad4 EAS

AF:

0.615

Gnomad4 SAS

AF:

0.519

Gnomad4 FIN

AF:

0.519

Gnomad4 NFE

AF:

0.499

Gnomad4 OTH

AF:

0.562

Alfa

AF:

0.508

Hom.:

29740

Bravo

AF:

0.537

Asia WGS

AF:

0.602

AC:

2096

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.6

DANN

Benign

0.51

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over