rs768758510

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001131.3(CRISP1):​c.712T>G​(p.Cys238Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C238S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

CRISP1
NM_001131.3 missense

Scores

6
6
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.81
Variant links:
Genes affected
CRISP1 (HGNC:304): (cysteine rich secretory protein 1) Fertilization consists of a sequence of specific cell-cell interactions culminating in the fusion of the sperm and egg plasma membranes. Recognition, binding, and fusion occur through the interaction of complementary molecules that are localized to specific domains of the sperm and egg plasma membranes. In the sperm, the postacrosomal region or equatorial segment is involved in sperm-egg plasma membrane fusion. The protein encoded by this gene is a member of the cysteine-rich secretory protein (CRISP) family. It is expressed in the epididymis, is secreted into the epididymal lumen, and binds to the postacrosomal region of the sperm head, where it plays a role in sperm-egg fusion. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.983

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRISP1NM_001131.3 linkc.712T>G p.Cys238Gly missense_variant Exon 8 of 8 ENST00000335847.9 NP_001122.2 P54107-1A0A0K0K1I1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CRISP1ENST00000335847.9 linkc.712T>G p.Cys238Gly missense_variant Exon 8 of 8 1 NM_001131.3 ENSP00000338276.4 P54107-1
CRISP1ENST00000505118.1 linkc.712T>G p.Cys238Gly missense_variant Exon 8 of 8 1 ENSP00000427589.1 P54107-1
CRISP1ENST00000507853 linkc.*86T>G 3_prime_UTR_variant Exon 7 of 7 1 ENSP00000425020.1 P54107-2
CRISP1ENST00000329411 linkc.*86T>G 3_prime_UTR_variant Exon 6 of 6 5 ENSP00000331317.5 P54107-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251294
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135808
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461532
Hom.:
0
Cov.:
30
AF XY:
0.00000550
AC XY:
4
AN XY:
727080
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.00
EpiControl
AF:
0.0000594

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.94
BayesDel_addAF
Benign
-0.0044
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
24
DANN
Benign
0.96
DEOGEN2
Uncertain
0.78
D;D
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.45
.;T
M_CAP
Benign
0.0049
T
MetaRNN
Pathogenic
0.98
D;D
MetaSVM
Benign
-0.96
T
MutationAssessor
Pathogenic
3.6
H;H
PrimateAI
Uncertain
0.50
T
PROVEAN
Pathogenic
-9.7
D;D
REVEL
Uncertain
0.32
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.69
MutPred
0.93
Loss of methylation at K239 (P = 0.016);Loss of methylation at K239 (P = 0.016);
MVP
0.40
MPC
0.11
ClinPred
1.0
D
GERP RS
5.1
Varity_R
0.95
gMVP
0.94

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.

Other links and lift over

dbSNP: rs768758510; hg19: chr6-49803067; API