Variant 8-75017426-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031461.6(CRISPLD1):c.1103A>G(p.Asn368Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000317 in 1,606,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

CRISPLD1
NM_031461.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.97

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12631038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRISPLD1	NM_031461.6 linkuse as main transcript	c.1103A>G	p.Asn368Ser	missense_variant	10/15	ENST00000262207.9	NP_113649.1	Q9H336-1
CRISPLD1	NM_001286777.2 linkuse as main transcript	c.545A>G	p.Asn182Ser	missense_variant	8/13		NP_001273706.1	Q9H336-2
CRISPLD1	NM_001286778.2 linkuse as main transcript	c.539A>G	p.Asn180Ser	missense_variant	9/14		NP_001273707.1	B7Z8V9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CRISPLD1	ENST00000262207.9 linkuse as main transcript	c.1103A>G	p.Asn368Ser	missense_variant	10/15	1	NM_031461.6	ENSP00000262207.4	Q9H336-1
CRISPLD1	ENST00000517786.1 linkuse as main transcript	c.545A>G	p.Asn182Ser	missense_variant	8/13	2		ENSP00000429746.1	Q9H336-2
CRISPLD1	ENST00000523524.5 linkuse as main transcript	c.539A>G	p.Asn180Ser	missense_variant	9/14	2		ENSP00000430105.1	B7Z8V9

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152172

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000370

AC:

AN:

243564

Hom.:

AF XY:

0.0000228

AC XY:

AN XY:

131574

show subpopulations

Gnomad AFR exome

AF:

0.000251

Gnomad AMR exome

AF:

0.0000307

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000559

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000269

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000275

AC:

AN:

1454300

Hom.:

Cov.:

AF XY:

0.0000263

AC XY:

AN XY:

723210

show subpopulations

Gnomad4 AFR exome

AF:

0.0000908

Gnomad4 AMR exome

AF:

0.0000233

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000763

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000574

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000247

AC:

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

Oct 10, 2023

The c.1103A>G (p.N368S) alteration is located in exon 10 (coding exon 9) of the CRISPLD1 gene. This alteration results from a A to G substitution at nucleotide position 1103, causing the asparagine (N) at amino acid position 368 to be replaced by a serine (S). 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

0.068

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.53

DEOGEN2

Benign

0.26

T;.;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.37

T;T;T

M_CAP

Uncertain

0.094

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

0.45

N;.;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.14

N;N;N

REVEL

Benign

0.27

Sift

Benign

0.46

T;T;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.18

MVP

0.82

MPC

0.15

ClinPred

0.015

GERP RS

4.1

Varity_R

0.027

gMVP

0.17

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.

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