5-1057500-A-G

Variant names:

• chr5-1057500-A-G
• rs2241606
• NM_006598.3:c.2997T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006598.3(SLC12A7):​c.2997T>C​(p.Ser999Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 1,612,428 control chromosomes in the GnomAD database, including 329,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (24252 hom., cov: 33)
  • Exomes 𝑓: 0.64 (305662 hom.)
• Consequence: SLC12A7 NM_006598.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.73
• Publications: 30 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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 5-1057500-A-G is Benign according to our data. Variant chr5-1057500-A-G is described in ClinVar as Benign. ClinVar VariationId is 1230308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.73 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.654 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A7	NM_006598.3	MANE Select	c.2997T>C	p.Ser999Ser	synonymous	Exon 22 of 24	NP_006589.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A7	ENST00000264930.10	TSL:1 MANE Select	c.2997T>C	p.Ser999Ser	synonymous	Exon 22 of 24	ENSP00000264930.5
	SLC12A7	ENST00000634447.1	TSL:5	c.2697T>C	p.Ser899Ser	synonymous	Exon 20 of 23	ENSP00000489285.1
	SLC12A7	ENST00000945163.1		c.3099T>C	p.Ser1033Ser	synonymous	Exon 23 of 26	ENSP00000615222.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82639 AN: 152006 Hom.: 24246 Cov.: 33

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.564

GnomAD2 exomes AF: 0.615 AC: 153697 AN: 250036 AF XY: 0.624

Gnomad AFR exome AF: 0.288

Gnomad AMR exome AF: 0.631

Gnomad ASJ exome AF: 0.519

Gnomad EAS exome AF: 0.508

Gnomad FIN exome AF: 0.633

Gnomad NFE exome AF: 0.664

Gnomad OTH exome AF: 0.637

GnomAD4 exome AF: 0.643 AC: 939479 AN: 1460304 Hom.: 305662 Cov.: 55 AF XY: 0.646 AC XY: 469380 AN XY: 726526

African (AFR) AF: 0.285 AC: 9524 AN: 33466

American (AMR) AF: 0.621 AC: 27754 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 13528 AN: 26100

East Asian (EAS) AF: 0.514 AC: 20390 AN: 39688

South Asian (SAS) AF: 0.663 AC: 57113 AN: 86206

European-Finnish (FIN) AF: 0.637 AC: 33378 AN: 52386

Middle Eastern (MID) AF: 0.665 AC: 3834 AN: 5764

European-Non Finnish (NFE) AF: 0.663 AC: 736808 AN: 1111666

Other (OTH) AF: 0.615 AC: 37150 AN: 60370

GnomAD4 genome AF: 0.543 AC: 82671 AN: 152124 Hom.: 24252 Cov.: 33 AF XY: 0.544 AC XY: 40456 AN XY: 74346

African (AFR) AF: 0.306 AC: 12713 AN: 41520

American (AMR) AF: 0.588 AC: 8984 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1825 AN: 3472

East Asian (EAS) AF: 0.508 AC: 2623 AN: 5162

South Asian (SAS) AF: 0.654 AC: 3153 AN: 4820

European-Finnish (FIN) AF: 0.635 AC: 6715 AN: 10576

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.659 AC: 44814 AN: 67964

Other (OTH) AF: 0.567 AC: 1200 AN: 2116

Alfa AF: 0.619 Hom.: 58004

Bravo AF: 0.525

Asia WGS AF: 0.604 AC: 2100 AN: 3478

EpiCase AF: 0.657

EpiControl AF: 0.657

ClinVar

ClinVar submissions as Germline

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	-0.95
CADD	Benign	0.0080
DANN	Benign	0.18
PhyloP100		-1.7
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: rs2241606; hg19: chr5-1057615; COSMIC: COSV53755063; COSMIC: COSV53755063;