8-75013999-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_031461.6(CRISPLD1):ā€‹c.523A>Gā€‹(p.Thr175Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

CRISPLD1
NM_031461.6 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.20
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.786

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CRISPLD1NM_031461.6 linkc.523A>G p.Thr175Ala missense_variant 5/15 ENST00000262207.9 NP_113649.1 Q9H336-1
CRISPLD1NM_001286778.2 linkc.-42A>G 5_prime_UTR_variant 4/14 NP_001273707.1 B7Z8V9
CRISPLD1NM_001286777.2 linkc.69-813A>G intron_variant NP_001273706.1 Q9H336-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CRISPLD1ENST00000262207.9 linkc.523A>G p.Thr175Ala missense_variant 5/151 NM_031461.6 ENSP00000262207.4 Q9H336-1
CRISPLD1ENST00000523524 linkc.-42A>G 5_prime_UTR_variant 4/142 ENSP00000430105.1 B7Z8V9
CRISPLD1ENST00000517786.1 linkc.69-813A>G intron_variant 2 ENSP00000429746.1 Q9H336-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460210
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
726456
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsDec 19, 2022The c.523A>G (p.T175A) alteration is located in exon 5 (coding exon 4) of the CRISPLD1 gene. This alteration results from a A to G substitution at nucleotide position 523, causing the threonine (T) at amino acid position 175 to be replaced by an alanine (A). 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
0.22
BayesDel_addAF
Benign
-0.021
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.036
D
MetaRNN
Pathogenic
0.79
D
MetaSVM
Benign
-1.2
T
MutationAssessor
Benign
1.0
L
PrimateAI
Uncertain
0.67
T
PROVEAN
Uncertain
-3.3
D
REVEL
Uncertain
0.33
Sift
Uncertain
0.020
D
Sift4G
Uncertain
0.042
D
Polyphen
1.0
D
Vest4
0.82
MutPred
0.37
Gain of sheet (P = 0.0827);
MVP
0.82
MPC
0.65
ClinPred
0.99
D
GERP RS
5.0
Varity_R
0.31
gMVP
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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.

Other links and lift over

dbSNP: rs1167817081; hg19: chr8-75926234; API