1-74198025-G-C

Variant names:

• chr1-74198025-G-C
• rs11806946
• ENST00000463724.1:n.123C>G

Variant summary

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

The ENST00000463724.1(LRRIQ3):​n.123C>G variant causes a non coding transcript exon 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRIQ3 ENST00000463724.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154
• Publications: 20 publications found

Genes affected

LRRIQ3 (HGNC:28318): (leucine rich repeats and IQ motif containing 3)

FPGT (HGNC:3825): (fucose-1-phosphate guanylyltransferase) L-fucose is a key sugar in glycoproteins and other complex carbohydrates since it may be involved in many of the functional roles of these macromolecules, such as in cell-cell recognition. The fucosyl donor for these fucosylated oligosaccharides is GDP-beta-L-fucose. There are two alternate pathways for the biosynthesis of GDP-fucose; the major pathway converts GDP-alpha-D-mannose to GDP-beta-L-fucose. The protein encoded by this gene participates in an alternate pathway that is present in certain mammalian tissues, such as liver and kidney, and appears to function as a salvage pathway to reutilize L-fucose arising from the turnover of glycoproteins and glycolipids. This pathway involves the phosphorylation of L-fucose to form beta-L-fucose-1-phosphate, and then condensation of the beta-L-fucose-1-phosphate with GTP by fucose-1-phosphate guanylyltransferase to form GDP-beta-L-fucose. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream TNNI3 interacting kinase (TNNI3K) gene. [provided by RefSeq, Dec 2010]

FPGT-TNNI3K (HGNC:42952): (FPGT-TNNI3K readthrough) Enables protein C-terminus binding activity; protein kinase activity; and troponin I binding activity. Involved in protein phosphorylation and regulation of heart contraction. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000463724.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRIQ3	NM_001105659.2	MANE Select	c.-30C>G		5_prime_UTR	Exon 1 of 8	NP_001099129.1
	LRRIQ3	NM_001322315.2		c.-30C>G		5_prime_UTR	Exon 1 of 8	NP_001309244.1
	FPGT	NM_003838.5	MANE Select	c.-254G>C		upstream_gene	N/A	NP_003829.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRIQ3	ENST00000463724.1	TSL:1	n.123C>G		non_coding_transcript_exon	Exon 1 of 2
	LRRIQ3	ENST00000354431.9	TSL:5 MANE Select	c.-30C>G		5_prime_UTR	Exon 1 of 8	ENSP00000346414.4
	LRRIQ3	ENST00000370911.7	TSL:1	c.-30C>G		5_prime_UTR	Exon 1 of 4	ENSP00000359948.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 522270 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 265466

African (AFR) AF: 0.00 AC: 0 AN: 13942

American (AMR) AF: 0.00 AC: 0 AN: 15752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13192

East Asian (EAS) AF: 0.00 AC: 0 AN: 29200

South Asian (SAS) AF: 0.00 AC: 0 AN: 33714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2044

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 359076

Other (OTH) AF: 0.00 AC: 0 AN: 27690

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.3
DANN	Benign	0.52
PhyloP100		0.15
PromoterAI		0.048	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11806946; hg19: chr1-74663709;