1-74198247-C-T

Variant names:

• chr1-74198247-C-T
• rs76672163
• NM_003838.5:c.-32C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003838.5(FPGT):​c.-32C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,609,582 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: 𝑓 0.00058 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000067 (0 hom.)
• Consequence: FPGT NM_003838.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 1 publications found

Genes affected

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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007730484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FPGT	NM_003838.5	c.-32C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	ENST00000370898.9	NP_003829.4
FPGT	NM_003838.5	c.-32C>T		5_prime_UTR_variant	Exon 1 of 4	ENST00000370898.9	NP_003829.4
LRRIQ3	NM_001105659.2	c.-252G>A		upstream_gene_variant		ENST00000354431.9	NP_001099129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FPGT	ENST00000370898.9	c.-32C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	1	NM_003838.5	ENSP00000359935.4
FPGT-TNNI3K	ENST00000557284.7	c.-32C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 27	2		ENSP00000450895.3
FPGT	ENST00000370898.9	c.-32C>T		5_prime_UTR_variant	Exon 1 of 4	1	NM_003838.5	ENSP00000359935.4
FPGT-TNNI3K	ENST00000557284.7	c.-32C>T		5_prime_UTR_variant	Exon 1 of 27	2		ENSP00000450895.3
LRRIQ3	ENST00000354431.9	c.-252G>A		upstream_gene_variant		5	NM_001105659.2	ENSP00000346414.4

Frequencies

GnomAD3 genomes AF: 0.000579 AC: 88 AN: 151856 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000133

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000177 AC: 44 AN: 248848 AF XY: 0.0000891

Gnomad AFR exome AF: 0.00199

Gnomad AMR exome AF: 0.000233

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000356

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000665 AC: 97 AN: 1457610 Hom.: 0 Cov.: 31 AF XY: 0.0000566 AC XY: 41 AN XY: 724562

African (AFR) AF: 0.00186 AC: 62 AN: 33410

American (AMR) AF: 0.000224 AC: 10 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26044

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.00 AC: 0 AN: 86110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5208

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1109440

Other (OTH) AF: 0.0000332 AC: 2 AN: 60156

GnomAD4 genome AF: 0.000579 AC: 88 AN: 151972 Hom.: 0 Cov.: 32 AF XY: 0.000552 AC XY: 41 AN XY: 74300

African (AFR) AF: 0.00202 AC: 84 AN: 41530

American (AMR) AF: 0.000133 AC: 2 AN: 15014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.0000855 Hom.: 0

Bravo AF: 0.000763

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000214 AC: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Uncertain	0.12
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.099	T;.;.
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.48	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.0077	T;T;T
PhyloP100		-0.21
PROVEAN	Benign	-0.57	N;N;N
Sift	Benign	0.044	D;D;D
Vest4		0.24
MVP		0.72
MPC		0.023
GERP RS		0.59
PromoterAI		0.00080	Neutral
Varity_R		0.054
gMVP		0.34
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs76672163; hg19: chr1-74663931;