dbSNP rs371100188: CRISPLD1:p.Thr79Pro (chr8-74986222-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031461.6(CRISPLD1):c.235A>C(p.Thr79Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CRISPLD1
NM_031461.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.36

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040576637).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRISPLD1	NM_031461.6 link	c.235A>C	p.Thr79Pro	missense_variant	Exon 2 of 15	ENST00000262207.9	NP_113649.1	Q9H336-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRISPLD1	ENST00000262207.9 link	c.235A>C	p.Thr79Pro	missense_variant	Exon 2 of 15	1	NM_031461.6	ENSP00000262207.4	Q9H336-1
CRISPLD1	ENST00000520277.1 link	c.235A>C	p.Thr79Pro	missense_variant	Exon 3 of 4	5		ENSP00000430504.1	E5RJS4
CRISPLD1	ENST00000519798.1 link	n.511+105A>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000616

AC:

AN:

1461712

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727172

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:

0.0000937

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.000461

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.39

DEOGEN2

Benign

0.011

T;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.041

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.3

N;.

PrimateAI

Benign

0.48

PROVEAN

Benign

4.0

N;N

REVEL

Benign

0.088

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.13

MVP

0.57

MPC

0.25

ClinPred

0.018

GERP RS

1.5

Varity_R

0.15

gMVP

0.54

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over