NM_000341.4:c.1701G>A

Variant names:

• chr2-44320282-G-A
• rs904926333
• NM_000341.4:c.1701G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_000341.4(SLC3A1):​c.1701G>A​(p.Arg567Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC3A1 NM_000341.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.558
• Publications: 1 publications found

Genes affected

SLC3A1 (HGNC:11025): (solute carrier family 3 member 1) This gene encodes a type II membrane glycoprotein which is one of the components of the renal amino acid transporter which transports neutral and basic amino acids in the renal tubule and intestinal tract. Mutations and deletions in this gene are associated with cystinuria. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

PREPL (HGNC:30228): (prolyl endopeptidase like) The protein encoded by this gene belongs to the prolyl oligopeptidase subfamily of serine peptidases. Mutations in this gene have been associated with hypotonia-cystinuria syndrome, also known as the 2p21 deletion syndrome. Several alternatively spliced transcript variants encoding either the same or different isoforms have been described for this gene.[provided by RefSeq, Jan 2010]

PREPL Gene-Disease associations (from GenCC):

• hypotonia-cystinuria syndrome

  Inheritance: AR Classification: STRONG Submitted by: G2P
• myasthenic syndrome, congenital, 22

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina, PanelApp Australia

ENSG00000285542 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 2-44320282-G-A is Benign according to our data. Variant chr2-44320282-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 711667.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.558 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000341.4. 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
	SLC3A1	NM_000341.4	MANE Select	c.1701G>A	p.Arg567Arg	synonymous	Exon 10 of 10	NP_000332.2	Q07837-1
	PREPL	NM_001171613.2	MANE Select	c.*1074C>T		3_prime_UTR	Exon 14 of 14	NP_001165084.1	Q4J6C6-4
	PREPL	NM_001171603.1		c.*1074C>T		3_prime_UTR	Exon 15 of 15	NP_001165074.1	Q4J6C6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC3A1	ENST00000260649.11	TSL:1 MANE Select	c.1701G>A	p.Arg567Arg	synonymous	Exon 10 of 10	ENSP00000260649.6	Q07837-1
	SLC3A1	ENST00000409380.5	TSL:1	c.867G>A	p.Arg289Arg	synonymous	Exon 7 of 7	ENSP00000386709.1	Q07837-2
	SLC3A1	ENST00000409740.3	TSL:1	c.594G>A	p.Arg198Arg	synonymous	Exon 4 of 4	ENSP00000386677.3	Q07837-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.6
DANN	Benign	0.83
PhyloP100		0.56
Mutation Taster		=93/7	polymorphism

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: rs904926333; hg19: chr2-44547421;