17-44967711-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006688.5(C1QL1):​c.338C>T​(p.Ala113Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000323 in 1,609,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

C1QL1
NM_006688.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.13
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.043845385).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
C1QL1NM_006688.5 linkuse as main transcriptc.338C>T p.Ala113Val missense_variant 1/2 ENST00000253407.4 NP_006679.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
C1QL1ENST00000253407.4 linkuse as main transcriptc.338C>T p.Ala113Val missense_variant 1/21 NM_006688.5 ENSP00000253407 P1
NMT1ENST00000678938.1 linkuse as main transcriptc.-110+9649G>A intron_variant ENSP00000503621 P30419-2

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152030
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000388
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000920
AC:
22
AN:
239136
Hom.:
0
AF XY:
0.0000992
AC XY:
13
AN XY:
131022
show subpopulations
Gnomad AFR exome
AF:
0.0000669
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000612
Gnomad SAS exome
AF:
0.000296
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000170
GnomAD4 exome
AF:
0.0000309
AC:
45
AN:
1457676
Hom.:
0
Cov.:
32
AF XY:
0.0000317
AC XY:
23
AN XY:
725140
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.000244
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.000216
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152148
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000389
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ExAC
AF:
0.0000751
AC:
9
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 31, 2023The c.338C>T (p.A113V) alteration is located in exon 1 (coding exon 1) of the C1QL1 gene. This alteration results from a C to T substitution at nucleotide position 338, causing the alanine (A) at amino acid position 113 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.43
T
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.80
FATHMM_MKL
Benign
0.20
N
LIST_S2
Uncertain
0.89
D
M_CAP
Uncertain
0.25
D
MetaRNN
Benign
0.044
T
MetaSVM
Benign
-0.45
T
MutationAssessor
Benign
0.70
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.46
T
PROVEAN
Benign
0.020
N
REVEL
Benign
0.12
Sift
Benign
0.38
T
Sift4G
Benign
0.55
T
Polyphen
0.026
B
Vest4
0.13
MutPred
0.41
Loss of sheet (P = 0.0142);
MVP
0.48
ClinPred
0.0081
T
GERP RS
3.6
Varity_R
0.051
gMVP
0.23

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs375251255; hg19: chr17-43045079; API