rs708727

Variant names:

• chr1-205798757-G-A
• rs708727
• NM_173854.6:c.756C>T

Variant summary

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

The NM_173854.6(SLC41A1):​c.756C>T​(p.Asn252Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,613,886 control chromosomes in the GnomAD database, including 117,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (8147 hom., cov: 32)
  • Exomes 𝑓: 0.37 (109043 hom.)
• Consequence: SLC41A1 NM_173854.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.410
• Publications: 60 publications found

Genes affected

SLC41A1 (HGNC:19429): (solute carrier family 41 member 1) Enables magnesium ion transmembrane transporter activity and magnesium:sodium antiporter activity. Involved in cellular magnesium ion homeostasis; cellular response to magnesium ion; and magnesium ion transmembrane transport. Located in basolateral plasma membrane. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

SLC41A1 Gene-Disease associations (from GenCC):

• kidney disorder

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• nephronophthisis-like nephropathy 2

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 1-205798757-G-A is Benign according to our data. Variant chr1-205798757-G-A is described in ClinVar as Benign. ClinVar VariationId is 1553777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173854.6. 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
	SLC41A1	NM_173854.6	MANE Select	c.756C>T	p.Asn252Asn	synonymous	Exon 6 of 11	NP_776253.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC41A1	ENST00000367137.4	TSL:1 MANE Select	c.756C>T	p.Asn252Asn	synonymous	Exon 6 of 11	ENSP00000356105.3
	SLC41A1	ENST00000468057.5	TSL:2	n.552C>T		non_coding_transcript_exon	Exon 5 of 10

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43100 AN: 151892 Hom.: 8152 Cov.: 32

Gnomad AFR AF: 0.0768

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.00310

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.316

GnomAD2 exomes AF: 0.296 AC: 74486 AN: 251468 AF XY: 0.301

Gnomad AFR exome AF: 0.0653

Gnomad AMR exome AF: 0.181

Gnomad ASJ exome AF: 0.372

Gnomad EAS exome AF: 0.000870

Gnomad FIN exome AF: 0.442

Gnomad NFE exome AF: 0.414

Gnomad OTH exome AF: 0.336

GnomAD4 exome AF: 0.370 AC: 540921 AN: 1461876 Hom.: 109043 Cov.: 65 AF XY: 0.365 AC XY: 265123 AN XY: 727242

African (AFR) AF: 0.0606 AC: 2029 AN: 33480

American (AMR) AF: 0.189 AC: 8432 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 9823 AN: 26136

East Asian (EAS) AF: 0.000831 AC: 33 AN: 39700

South Asian (SAS) AF: 0.158 AC: 13623 AN: 86258

European-Finnish (FIN) AF: 0.444 AC: 23736 AN: 53416

Middle Eastern (MID) AF: 0.295 AC: 1702 AN: 5768

European-Non Finnish (NFE) AF: 0.415 AC: 461168 AN: 1111998

Other (OTH) AF: 0.337 AC: 20375 AN: 60396

GnomAD4 genome AF: 0.283 AC: 43085 AN: 152010 Hom.: 8147 Cov.: 32 AF XY: 0.279 AC XY: 20711 AN XY: 74274

African (AFR) AF: 0.0766 AC: 3179 AN: 41486

American (AMR) AF: 0.268 AC: 4094 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1277 AN: 3468

East Asian (EAS) AF: 0.00310 AC: 16 AN: 5154

South Asian (SAS) AF: 0.150 AC: 725 AN: 4832

European-Finnish (FIN) AF: 0.445 AC: 4688 AN: 10544

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28055 AN: 67938

Other (OTH) AF: 0.312 AC: 658 AN: 2106

Alfa AF: 0.372 Hom.: 25888

Bravo AF: 0.260

Asia WGS AF: 0.0690 AC: 244 AN: 3478

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	-0.47
CADD	Benign	3.1
DANN	Benign	0.80
PhyloP100		-0.41
Mutation Taster		=97/3	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: rs708727; hg19: chr1-205767885; COSMIC: COSV65650053; COSMIC: COSV65650053;