Genetic Variant SLC28A1:p.Leu140_Lys141insVal (chr15-84895080-C-CTTG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PM4_SupportingBP6BA1

The NM_004213.5(SLC28A1):c.419_420insTGT(p.Leu140_Lys141insVal) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,613,752 control chromosomes in the GnomAD database, including 66,416 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.29 ( 6491 hom., cov: 16)

Exomes 𝑓: 0.28 ( 59925 hom. )

Consequence

SLC28A1
NM_004213.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.123

Variant links:

Genes affected

SLC28A1 (HGNC:11001): (solute carrier family 28 member 1) Enables azole transmembrane transporter activity; cytidine transmembrane transporter activity; and uridine transmembrane transporter activity. Involved in azole transmembrane transport; nucleoside transport; and pyrimidine-containing compound transmembrane transport. Located in cytosol; nuclear speck; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC28A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_004213.5. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 15-84895080-C-CTTG is Benign according to our data. Variant chr15-84895080-C-CTTG is described in ClinVar as [Benign]. Clinvar id is 3060075.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A1	NM_004213.5 link	c.419_420insTGT	p.Leu140_Lys141insVal	disruptive_inframe_insertion	Exon 6 of 19	ENST00000394573.6	NP_004204.3	O00337-1B7Z3L5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC28A1	ENST00000394573.6 link	c.419_420insTGT	p.Leu140_Lys141insVal	disruptive_inframe_insertion	Exon 6 of 19	1	NM_004213.5	ENSP00000378074.1	O00337-1
SLC28A1	ENST00000286749.3 link	c.419_420insTGT	p.Leu140_Lys141insVal	disruptive_inframe_insertion	Exon 5 of 18	1		ENSP00000286749.3	O00337-1
SLC28A1	ENST00000338602.6 link	c.419_420insTGT	p.Leu140_Lys141insVal	disruptive_inframe_insertion	Exon 6 of 7	1		ENSP00000341629.2	O00337-2
SLC28A1	ENST00000538177.5 link	c.419_420insTGT	p.Leu140_Lys141insVal	disruptive_inframe_insertion	Exon 5 of 15	2		ENSP00000443752.1	B7Z3L6

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

44043

AN:

151836

Hom.:

6486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.299

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.354

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.322

GnomAD3 exomes

AF:

0.273

AC:

68628

AN:

250936

Hom.:

9890

AF XY:

0.274

AC XY:

37253

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.297

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.363

Gnomad EAS exome

AF:

0.203

Gnomad SAS exome

AF:

0.203

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.306

Gnomad OTH exome

AF:

0.303

GnomAD4 exome

AF:

0.284

AC:

414658

AN:

1461798

Hom.:

59925

Cov.:

AF XY:

0.282

AC XY:

205109

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.303

Gnomad4 AMR exome

AF:

0.215

Gnomad4 ASJ exome

AF:

0.370

Gnomad4 EAS exome

AF:

0.196

Gnomad4 SAS exome

AF:

0.201

Gnomad4 FIN exome

AF:

0.297

Gnomad4 NFE exome

AF:

0.292

Gnomad4 OTH exome

AF:

0.294

GnomAD4 genome

AF:

0.290

AC:

44071

AN:

151954

Hom.:

6491

Cov.:

AF XY:

0.287

AC XY:

21337

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.299

Gnomad4 AMR

AF:

0.256

Gnomad4 ASJ

AF:

0.354

Gnomad4 EAS

AF:

0.199

Gnomad4 SAS

AF:

0.190

Gnomad4 FIN

AF:

0.291

Gnomad4 NFE

AF:

0.302

Gnomad4 OTH

AF:

0.321

Alfa

AF:

0.243

Hom.:

816

Bravo

AF:

0.290

Asia WGS

AF:

0.226

AC:

787

AN:

3478

EpiCase

AF:

0.313

EpiControl

AF:

0.317

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SLC28A1-related disorder

Benign:1

Oct 30, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over