NM_006688.5:c.349G>T

Variant names:

• chr17-44967700-C-A
• NM_006688.5:c.349G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006688.5(C1QL1):​c.349G>T​(p.Gly117Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: C1QL1 NM_006688.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.83
• Publications: 0 publications found

Genes affected

C1QL1 (HGNC:24182): (complement C1q like 1) Predicted to enable signaling receptor binding activity. Predicted to act upstream of or within maintenance of synapse structure; motor learning; and neuron remodeling. Predicted to be located in several cellular components, including climbing fiber; presynapse; and synaptic cleft. Predicted to be part of collagen trimer. [provided by Alliance of Genome Resources, Apr 2022]

NMT1 (HGNC:7857): (N-myristoyltransferase 1) Myristate, a rare 14-carbon saturated fatty acid, is cotranslationally attached by an amide linkage to the N-terminal glycine residue of cellular and viral proteins with diverse functions. N-myristoyltransferase (NMT; EC 2.3.1.97) catalyzes the transfer of myristate from CoA to proteins. N-myristoylation appears to be irreversible and is required for full expression of the biologic activities of several N-myristoylated proteins, including the alpha subunit of the signal-transducing guanine nucleotide-binding protein (G protein) GO (GNAO1; MIM 139311) (Duronio et al., 1992 [PubMed 1570339]).[supplied by OMIM, Nov 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.812

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006688.5. 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
	C1QL1	NM_006688.5	MANE Select	c.349G>T	p.Gly117Cys	missense	Exon 1 of 2	NP_006679.1	O75973

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QL1	ENST00000253407.4	TSL:1 MANE Select	c.349G>T	p.Gly117Cys	missense	Exon 1 of 2	ENSP00000253407.2	O75973
	C1QL1	ENST00000718438.1		c.439G>T	p.Gly147Cys	missense	Exon 1 of 2	ENSP00000520823.1	A0ABB0MVI4
	NMT1	ENST00000678938.1		c.-110+9638C>A		intron	N/A	ENSP00000503621.1	P30419-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.67	T
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.8
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.8	D
REVEL	Pathogenic	0.68
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.63
MutPred		0.54		Loss of sheet (P = 0.0054)
MVP		0.77
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.73
gMVP		0.66

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

hg19: chr17-43045068;