Variant 8-75013990-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_031461.6(CRISPLD1):c.514G>A(p.Val172Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000814 in 1,608,682 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 (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

CRISPLD1
NM_031461.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.87

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 made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.815

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CRISPLD1	NM_031461.6 linkuse as main transcript	c.514G>A	p.Val172Met	missense_variant	5/15	ENST00000262207.9
CRISPLD1	NM_001286778.2 linkuse as main transcript	c.-51G>A		5_prime_UTR_variant	4/14
CRISPLD1	NM_001286777.2 linkuse as main transcript	c.69-822G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRISPLD1	ENST00000262207.9 linkuse as main transcript	c.514G>A	p.Val172Met	missense_variant	5/15	1	NM_031461.6	P1	Q9H336-1
CRISPLD1	ENST00000523524.5 linkuse as main transcript	c.-51G>A		5_prime_UTR_variant	4/14	2
CRISPLD1	ENST00000517786.1 linkuse as main transcript	c.69-822G>A		intron_variant		2			Q9H336-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000957

AC:

AN:

250850

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135608

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 SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000705

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000879

AC:

128

AN:

1456750

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

724936

show subpopulations

Gnomad4 AFR exome

AF:

0.0000900

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000546

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000641

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151932

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74182

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000783

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.000123

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

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 submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The c.514G>A (p.V172M) alteration is located in exon 5 (coding exon 4) of the CRISPLD1 gene. This alteration results from a G to A substitution at nucleotide position 514, causing the valine (V) at amino acid position 172 to be replaced by a methionine (M). 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

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.035

MetaRNN

Pathogenic

0.81

MetaSVM

Benign

-0.64

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.49

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.96

MutPred

0.58

Loss of catalytic residue at V172 (P = 0.0024);

MVP

0.71

MPC

0.75

ClinPred

0.65

GERP RS

4.8

Varity_R

0.42

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over