NM_006688.5:c.676G>C

Variant names:

• chr17-44960289-C-G
• NM_006688.5:c.676G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006688.5(C1QL1):​c.676G>C​(p.Ala226Pro) variant causes a missense 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 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: 1.30
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20582047).

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.676G>C	p.Ala226Pro	missense	Exon 2 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.676G>C	p.Ala226Pro	missense	Exon 2 of 2	ENSP00000253407.2	O75973
	C1QL1	ENST00000718438.1		c.766G>C	p.Ala256Pro	missense	Exon 2 of 2	ENSP00000520823.1	A0ABB0MVI4
	NMT1	ENST00000678938.1		c.-110+2227C>G		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	Benign	0.17
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-0.34	N
PhyloP100		1.3
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.14	N
REVEL	Uncertain	0.38
Sift	Benign	0.22	T
Sift4G	Benign	0.82	T
Polyphen		0.018	B
Vest4		0.18
MutPred		0.42		Loss of catalytic residue at A226 (P = 0.0215)
MVP		0.45
ClinPred		0.91	D
GERP RS		4.7
Varity_R		0.36
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: chr17-43037657;