Genetic Variant NM_080669.6:c.*4635dupT (chr17-28395020-G-GA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_080669.6(SLC46A1):c.*4635dupT 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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.395

Publications

3 publications found

Variant links:

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]

SLC46A1 links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC46A1	NM_080669.6 link	c.*4635dupT		3_prime_UTR_variant	Exon 5 of 5	ENST00000612814.5	NP_542400.2	Q96NT5-1A0A024QZ15
SARM1	NM_015077.4 link	c.1924-873dupA		intron_variant	Intron 7 of 8	ENST00000585482.6	NP_055892.2	Q6SZW1-1Q05B42Q0D2N8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC46A1	ENST00000612814.5 link	c.*4635dupT		3_prime_UTR_variant	Exon 5 of 5	2	NM_080669.6	ENSP00000480703.1		Q96NT5-1
SARM1	ENST00000585482.6 link	c.1924-873dupA		intron_variant	Intron 7 of 8	1	NM_015077.4	ENSP00000468032.2		Q6SZW1-1

Frequencies

GnomAD3 genomes

AF:

0.599

AC:

88424

AN:

147572

Hom.:

26567

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.599

AC:

88454

AN:

147644

Hom.:

26564

Cov.:

AF XY:

0.594

AC XY:

42610

AN XY:

71716

show subpopulations

African (AFR)

AF:

0.686

AC:

27586

AN:

40222

American (AMR)

AF:

0.631

AC:

9397

AN:

14890

Ashkenazi Jewish (ASJ)

AF:

0.567

AC:

1949

AN:

3438

East Asian (EAS)

AF:

0.724

AC:

3694

AN:

5100

South Asian (SAS)

AF:

0.525

AC:

2432

AN:

4630

European-Finnish (FIN)

AF:

0.445

AC:

4124

AN:

9266

Middle Eastern (MID)

AF:

0.667

AC:

192

AN:

288

European-Non Finnish (NFE)

AF:

0.558

AC:

37305

AN:

66856

Other (OTH)

AF:

0.621

AC:

1279

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1680

3360

5039

6719

8399

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.305

Hom.:

506

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital defect of folate absorption

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.40

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_080669.6:c.*4635dupT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over