Genetic Variant CRISPLD1:p.Asp89Glu (chr8-75012441-T-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_031461.6(CRISPLD1):c.267T>A(p.Asp89Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,455,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D89V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CRISPLD1
NM_031461.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86

Publications

1 publications found

Variant links:

Genes affected

CRISPLD1 (HGNC:18206): (cysteine rich secretory protein LCCL domain containing 1) Involved in face morphogenesis. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

CRISPLD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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, 0.794

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031461.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRISPLD1	NM_031461.6	MANE Select	c.267T>A	p.Asp89Glu	missense	Exon 3 of 15	NP_113649.1	Q9H336-1
CRISPLD1	NM_001286777.2		c.-176T>A		5_prime_UTR	Exon 2 of 13	NP_001273706.1	Q9H336-2
CRISPLD1	NM_001286778.2		c.-298T>A		5_prime_UTR	Exon 2 of 14	NP_001273707.1	B7Z8V9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRISPLD1	ENST00000262207.9	TSL:1 MANE Select	c.267T>A	p.Asp89Glu	missense	Exon 3 of 15	ENSP00000262207.4	Q9H336-1
CRISPLD1	ENST00000959492.1		c.267T>A	p.Asp89Glu	missense	Exon 3 of 15	ENSP00000629551.1
CRISPLD1	ENST00000916000.1		c.267T>A	p.Asp89Glu	missense	Exon 3 of 15	ENSP00000586059.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

250958

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1455878

Hom.:

Cov.:

AF XY:

0.00000690

AC XY:

AN XY:

724654

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33330

American (AMR)

AF:

0.00

AC:

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26048

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.00

AC:

AN:

86136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00000542

AC:

AN:

1106768

Other (OTH)

AF:

0.0000166

AC:

AN:

60166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.082

MetaRNN

Pathogenic

0.79

MetaSVM

Benign

-0.64

MutationAssessor

Pathogenic

4.0

PhyloP100

1.9

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.51

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.95

MutPred

0.68

Gain of disorder (P = 0.0915)

MVP

0.84

MPC

0.56

ClinPred

0.99

GERP RS

3.9

Varity_R

0.69

gMVP

0.78

Mutation Taster

=28/72

disease causing

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over