chr17-44967793-C-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006688.5(C1QL1):c.256G>T(p.Asp86Tyr) 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 1,456,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

C1QL1
NM_006688.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.15

Publications

0 publications found

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]

C1QL1 links:

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]

NMT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17896384).

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.256G>T	p.Asp86Tyr	missense	Exon 1 of 2	NP_006679.1	O75973

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C1QL1	ENST00000253407.4	TSL:1 MANE Select	c.256G>T	p.Asp86Tyr	missense	Exon 1 of 2	ENSP00000253407.2	O75973
C1QL1	ENST00000718438.1		c.346G>T	p.Asp116Tyr	missense	Exon 1 of 2	ENSP00000520823.1	A0ABB0MVI4
NMT1	ENST00000678938.1		c.-110+9731C>A		intron	N/A	ENSP00000503621.1	P30419-2

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000391

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000918

AC:

AN:

54462

AF XY:

0.0000639

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000707

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000299

AC:

AN:

1304662

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

641120

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25898

American (AMR)

AF:

0.0000530

AC:

AN:

18884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19844

East Asian (EAS)

AF:

0.000312

AC:

AN:

32054

South Asian (SAS)

AF:

0.000181

AC:

AN:

66162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3816

European-Non Finnish (NFE)

AF:

0.00000285

AC:

AN:

1050920

Other (OTH)

AF:

0.000241

AC:

AN:

54038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000527

AC:

AN:

151916

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41498

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000393

AC:

AN:

5094

South Asian (SAS)

AF:

0.000622

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67880

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000475

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000358

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.76

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.66

M_CAP

Pathogenic

0.41

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.1

PhyloP100

1.1

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.9

REVEL

Benign

0.15

Sift

Uncertain

0.020

Sift4G

Benign

0.070

Polyphen

0.0010

Vest4

0.25

MutPred

0.43

Gain of phosphorylation at D86 (P = 0.0081)

MVP

0.42

ClinPred

0.093

GERP RS

2.2

Varity_R

0.24

gMVP

0.34

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over