17-28394926-TG-T

Position:

• chr17-28394926-TG-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_080669.6(SLC46A1):​c.*4729delC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00217 in 152,096 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC46A1 NM_080669.6 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.543

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]

SARM1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC46A1	NM_080669.6	c.*4729delC		3_prime_UTR_variant	5/5	ENST00000612814.5	NP_542400.2
SARM1	NM_015077.4	c.1924-978delG		intron_variant		ENST00000585482.6	NP_055892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC46A1	ENST00000612814	c.*4729delC		3_prime_UTR_variant	5/5	2	NM_080669.6	ENSP00000480703.1
SARM1	ENST00000585482.6	c.1924-978delG		intron_variant		1	NM_015077.4	ENSP00000468032.2

Frequencies

GnomAD3 genomes AF: 0.00217 AC: 330 AN: 151978 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0278

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.00144

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.00217 AC: 330 AN: 152096 Hom.: 4 Cov.: 31 AF XY: 0.00332 AC XY: 247 AN XY: 74352

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0278

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.000702 Hom.: 0

Bravo AF: 0.000276

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital defect of folate absorption Uncertain:1

Uncertain significance, 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)		0.0		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: rs559270240; hg19: chr17-26721945;