Variant 8-75012946-G-C 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.434G>C(p.Ser145Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

CRISPLD1
NM_031461.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58

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=0.134801).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRISPLD1	NM_031461.6 linkuse as main transcript	c.434G>C	p.Ser145Thr	missense_variant	4/15	ENST00000262207.9	NP_113649.1	Q9H336-1
CRISPLD1	NM_001286777.2 linkuse as main transcript	c.-9G>C		5_prime_UTR_variant	3/13		NP_001273706.1	Q9H336-2
CRISPLD1	NM_001286778.2 linkuse as main transcript	c.-131G>C		5_prime_UTR_variant	3/14		NP_001273707.1	B7Z8V9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CRISPLD1	ENST00000262207.9 linkuse as main transcript	c.434G>C	p.Ser145Thr	missense_variant	4/15	1	NM_031461.6	ENSP00000262207.4	Q9H336-1
CRISPLD1	ENST00000517786.1 linkuse as main transcript	c.-9G>C		5_prime_UTR_variant	3/13	2		ENSP00000429746.1	Q9H336-2
CRISPLD1	ENST00000523524.5 linkuse as main transcript	c.-131G>C		5_prime_UTR_variant	3/14	2		ENSP00000430105.1	B7Z8V9

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151994

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Nov 24, 2024

The c.434G>C (p.S145T) alteration is located in exon 4 (coding exon 3) of the CRISPLD1 gene. This alteration results from a G to C substitution at nucleotide position 434, causing the serine (S) at amino acid position 145 to be replaced by a threonine (T). 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

0.066

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.17

DEOGEN2

Benign

0.010

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.60

M_CAP

Benign

0.017

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.33

PrimateAI

Benign

0.44

PROVEAN

Benign

0.090

REVEL

Benign

0.073

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.29

MutPred

0.50

Loss of disorder (P = 0.1092);

MVP

0.31

MPC

0.18

ClinPred

0.095

GERP RS

-0.28

Varity_R

0.048

gMVP

0.55

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