17-28395020-G-GA

Position:

• chr17-28395020-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_080669.6(SLC46A1):​c.*4635_*4636insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (26564 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: SLC46A1 NM_080669.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.395

Genes affected

SLC46A1 (HGNC:30521): (solute carrier family 46 member 1) This gene encodes a transmembrane proton-coupled folate transporter protein that facilitates the movement of folate and antifolate substrates across cell membranes, optimally in acidic pH environments. This protein is also expressed in the brain and choroid plexus where it transports folates into the central nervous system. This protein further functions as a heme transporter in duodenal enterocytes, and potentially in other tissues like liver and kidney. Its localization to the apical membrane or cytoplasm of intestinal cells is modulated by dietary iron levels. Mutations in this gene are associated with autosomal recessive hereditary folate malabsorption disease. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2013]

SARM1 (HGNC:17074): (sterile alpha and TIR motif containing 1) Enables NAD+ nucleotidase, cyclic ADP-ribose generating and identical protein binding activity. Involved in NAD catabolic process; positive regulation of neuron death; and response to axon injury. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-28395020-G-GA is Benign according to our data. Variant chr17-28395020-G-GA is described in ClinVar as [Benign]. Clinvar id is 322341.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC46A1	NM_080669.6	c.*4635_*4636insT		3_prime_UTR_variant	5/5	ENST00000612814.5	NP_542400.2
SARM1	NM_015077.4	c.1924-873dup		intron_variant		ENST00000585482.6	NP_055892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC46A1	ENST00000612814.5	c.*4635_*4636insT		3_prime_UTR_variant	5/5	2	NM_080669.6	ENSP00000480703	P1
SARM1	ENST00000585482.6	c.1924-873dup		intron_variant		1	NM_015077.4	ENSP00000468032	P1

Frequencies

GnomAD3 genomes AF: 0.599 AC: 88424 AN: 147572 Hom.: 26567 Cov.: 0

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.625

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.599 AC: 88454 AN: 147644 Hom.: 26564 Cov.: 0 AF XY: 0.594 AC XY: 42610 AN XY: 71716

Gnomad4 AFR AF: 0.686

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.621

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital defect of folate absorption Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs34879232; hg19: chr17-26722039;