rs60844753

Variant names:

• chr1-112956453-G-A
• rs60844753
• ENST00000416193.7:n.50G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-112956453-G-A
• chr1-112956453-G-C
• chr1-112956453-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000429288.2(SLC16A1):​c.-45+386C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 182,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: SLC16A1 ENST00000429288.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 3 publications found

Genes affected

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

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 Gene-Disease associations (from GenCC):

• ketoacidosis due to monocarboxylate transporter-1 deficiency

  Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• exercise-induced hyperinsulinism

  Inheritance: AD, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• disorder of fatty acid and ketone body metabolism

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• metabolic myopathy due to lactate transporter defect

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000429288.2. 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-AS1	NR_103743.1		n.39G>A		non_coding_transcript_exon	Exon 1 of 3
	SLC16A1-AS1	NR_103744.1		n.39G>A		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A1-AS1	ENST00000416193.7	TSL:1	n.50G>A		non_coding_transcript_exon	Exon 1 of 3
	SLC16A1-AS1	ENST00000428411.6	TSL:1	n.39G>A		non_coding_transcript_exon	Exon 1 of 3
	SLC16A1	ENST00000429288.2	TSL:3	c.-45+386C>T		intron	N/A	ENSP00000397106.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000164 AC: 3 AN: 182940 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 93258

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 5276

American (AMR) AF: 0.00 AC: 0 AN: 5226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6886

East Asian (EAS) AF: 0.00 AC: 0 AN: 17348

South Asian (SAS) AF: 0.00 AC: 0 AN: 1636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 990

European-Non Finnish (NFE) AF: 0.0000253 AC: 3 AN: 118372

Other (OTH) AF: 0.00 AC: 0 AN: 12140

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00131091), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.4
DANN	Benign	0.90
PhyloP100		-2.1
PromoterAI		-0.013	Neutral

Splicing

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

Other links and lift over

dbSNP: rs60844753; hg19: chr1-113499075;