Variant 8-75016623-G-C 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.786G>C(p.Gln262His) 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 1,461,290 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: 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: 0.257

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=0.3289938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CRISPLD1	NM_031461.6 linkuse as main transcript	c.786G>C	p.Gln262His	missense_variant	7/15	ENST00000262207.9
CRISPLD1	NM_001286777.2 linkuse as main transcript	c.228G>C	p.Gln76His	missense_variant	5/13
CRISPLD1	NM_001286778.2 linkuse as main transcript	c.222G>C	p.Gln74His	missense_variant	6/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRISPLD1	ENST00000262207.9 linkuse as main transcript	c.786G>C	p.Gln262His	missense_variant	7/15	1	NM_031461.6	P1	Q9H336-1
CRISPLD1	ENST00000517786.1 linkuse as main transcript	c.228G>C	p.Gln76His	missense_variant	5/13	2			Q9H336-2
CRISPLD1	ENST00000523524.5 linkuse as main transcript	c.222G>C	p.Gln74His	missense_variant	6/14	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251238

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461290

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726950

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

May 20, 2024

The c.786G>C (p.Q262H) alteration is located in exon 7 (coding exon 6) of the CRISPLD1 gene. This alteration results from a G to C substitution at nucleotide position 786, causing the glutamine (Q) at amino acid position 262 to be replaced by a histidine (H). 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

0.14

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.026

T;.;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.73

T;T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Uncertain

-0.10

MutationAssessor

Benign

1.4

L;.;.

MutationTaster

Benign

0.72

D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.27

Sift

Benign

0.11

T;T;T

Sift4G

Uncertain

0.056

T;T;T

Polyphen

0.85

P;.;.

Vest4

0.41

MutPred

0.19

Gain of loop (P = 0.0435);.;.;

MVP

0.87

MPC

0.50

ClinPred

0.33

GERP RS

1.9

Varity_R

0.045

gMVP

0.77

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