Variant 8-75016580-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_031461.6(CRISPLD1):c.743A>G(p.Tyr248Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CRISPLD1
NM_031461.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34503692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CRISPLD1	NM_031461.6 linkuse as main transcript	c.743A>G	p.Tyr248Cys	missense_variant	7/15	ENST00000262207.9
CRISPLD1	NM_001286777.2 linkuse as main transcript	c.185A>G	p.Tyr62Cys	missense_variant	5/13
CRISPLD1	NM_001286778.2 linkuse as main transcript	c.179A>G	p.Tyr60Cys	missense_variant	6/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRISPLD1	ENST00000262207.9 linkuse as main transcript	c.743A>G	p.Tyr248Cys	missense_variant	7/15	1	NM_031461.6	P1	Q9H336-1
CRISPLD1	ENST00000517786.1 linkuse as main transcript	c.185A>G	p.Tyr62Cys	missense_variant	5/13	2			Q9H336-2
CRISPLD1	ENST00000523524.5 linkuse as main transcript	c.179A>G	p.Tyr60Cys	missense_variant	6/14	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251002

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135680

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460768

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726716

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 21, 2023

The c.743A>G (p.Y248C) alteration is located in exon 7 (coding exon 6) of the CRISPLD1 gene. This alteration results from a A to G substitution at nucleotide position 743, causing the tyrosine (Y) at amino acid position 248 to be replaced by a cysteine (C). 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

0.13

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.20

T;.;.

Eigen

Benign

-0.049

Eigen_PC

Benign

-0.014

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Benign

-0.30

MutationAssessor

Benign

1.9

L;.;.

MutationTaster

Benign

0.66

N;N;N

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.7

D;D;N

REVEL

Benign

0.17

Sift

Benign

0.048

D;T;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.16

B;.;.

Vest4

0.32

MutPred

0.23

Loss of phosphorylation at Y248 (P = 0.0183);.;.;

MVP

0.92

MPC

0.33

ClinPred

0.79

GERP RS

4.9

Varity_R

0.097

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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