rs387906403

Variant names:

• chr1-112956192-C-T
• rs387906403
• NM_003051.4:c.-202G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_003051.4(SLC16A1):​c.-202G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC16A1 NM_003051.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.462
• Publications: 1 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-112956192-C-T is Pathogenic according to our data. Variant chr1-112956192-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 8916.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64). . Strength limited to SUPPORTING due to the PP5.

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.-202G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_003042.3
	SLC16A1	NM_003051.4	MANE Select	c.-202G>A		5_prime_UTR	Exon 1 of 5	NP_003042.3
	SLC16A1	NM_001166496.2		c.-961G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_001159968.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A1	ENST00000369626.8	TSL:1 MANE Select	c.-202G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000358640.4
	SLC16A1	ENST00000369626.8	TSL:1 MANE Select	c.-202G>A		5_prime_UTR	Exon 1 of 5	ENSP00000358640.4
	SLC16A1	ENST00000458229.6	TSL:2	c.-305G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000416167.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Exercise-induced hyperinsulinism (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Benign	0.92
PhyloP100		0.46
PromoterAI		0.49	Neutral
Mutation Taster		=105/195	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs387906403; hg19: chr1-113498814;