Genetic Variant SLC16A1:c.*1085delT (chr1-112912805-TA-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_003051.4(SLC16A1):c.*1085delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00766 in 136,438 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0077 ( 9 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

SLC16A1
NM_003051.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.312

Publications

1 publications found

Variant links:

Genes affected

SLC16A1 (HGNC:10922): (solute carrier family 16 member 1) The protein encoded by this gene is a proton-linked monocarboxylate transporter that catalyzes the movement of many monocarboxylates, such as lactate and pyruvate, across the plasma membrane. Mutations in this gene are associated with erythrocyte lactate transporter defect. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Oct 2009]

SLC16A1 links:

SLC16A1-AS1 (HGNC:49445): (SLC16A1 antisense RNA 1)

SLC16A1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00766 (1045/136438) while in subpopulation AFR AF = 0.0232 (865/37318). AF 95% confidence interval is 0.0219. There are 9 homozygotes in GnomAd4. There are 497 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 9 AD,AR,Unknown,SD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003051.4. 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
	SLC16A1	NM_003051.4	MANE Select	c.*1085delT		3_prime_UTR	Exon 5 of 5	NP_003042.3
	SLC16A1	NM_001166496.2		c.*1085delT		3_prime_UTR	Exon 5 of 5	NP_001159968.1	P53985-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC16A1	ENST00000369626.8	TSL:1 MANE Select	c.*1085delT	3_prime_UTR	Exon 5 of 5	ENSP00000358640.4	P53985-1
SLC16A1	ENST00000429288.2	TSL:3	c.*1085delT	3_prime_UTR	Exon 5 of 5	ENSP00000397106.2	P53985-1
SLC16A1	ENST00000443580.6	TSL:3	c.*1085delT	3_prime_UTR	Exon 5 of 5	ENSP00000399104.2	P53985-1

Frequencies

GnomAD3 genomes

AF:

0.00760

AC:

1037

AN:

136404

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0230

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00422

Gnomad ASJ

AF:

0.00250

Gnomad EAS

AF:

0.00104

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00231

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00139

Gnomad OTH

AF:

0.00330

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:

0.00766

AC:

1045

AN:

136438

Hom.:

Cov.:

AF XY:

0.00753

AC XY:

497

AN XY:

65990

show subpopulations

African (AFR)

AF:

0.0232

AC:

865

AN:

37318

American (AMR)

AF:

0.00415

AC:

AN:

13508

Ashkenazi Jewish (ASJ)

AF:

0.00250

AC:

AN:

3206

East Asian (EAS)

AF:

0.00104

AC:

AN:

4808

South Asian (SAS)

AF:

0.00

AC:

AN:

4334

European-Finnish (FIN)

AF:

0.00231

AC:

AN:

7788

Middle Eastern (MID)

AF:

0.00

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.00139

AC:

AN:

62528

Other (OTH)

AF:

0.00327

AC:

AN:

1834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

126

168

210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000820

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hyperinsulinism, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.31

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-112912805-TAAAAAAAA-TAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over