1-205795005-G-A

Variant names:

• chr1-205795005-G-A
• rs748119784
• NM_173854.6:c.1221C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_173854.6(SLC41A1):​c.1221C>T​(p.Arg407Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R407R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC41A1 NM_173854.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 0 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, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=-0.091 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC41A1	NM_173854.6	MANE Select	c.1221C>T	p.Arg407Arg	synonymous	Exon 10 of 11	NP_776253.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC41A1	ENST00000367137.4	TSL:1 MANE Select	c.1221C>T	p.Arg407Arg	synonymous	Exon 10 of 11	ENSP00000356105.3	Q8IVJ1
	SLC41A1	ENST00000911130.1		c.1269C>T	p.Arg423Arg	synonymous	Exon 10 of 11	ENSP00000581189.1
	SLC41A1	ENST00000948596.1		c.1257C>T	p.Arg419Arg	synonymous	Exon 10 of 11	ENSP00000618655.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461736 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727172

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.9
DANN	Benign	0.65
PhyloP100		-0.091
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs748119784; hg19: chr1-205764133;