Genetic Variant CRISP1:p.Ser121Asn (chr6-49846593-C-T) – 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_001131.3(CRISP1):c.362G>A(p.Ser121Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,613,592 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S121I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

CRISP1
NM_001131.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.347

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]

CRISP1 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=0.018442929).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRISP1	NM_001131.3 link	c.362G>A	p.Ser121Asn	missense_variant	Exon 5 of 8	ENST00000335847.9	NP_001122.2	P54107-1A0A0K0K1I1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRISP1	ENST00000335847.9 link	c.362G>A	p.Ser121Asn	missense_variant	Exon 5 of 8	1	NM_001131.3	ENSP00000338276.4	P54107-1
CRISP1	ENST00000505118.1 link	c.362G>A	p.Ser121Asn	missense_variant	Exon 5 of 8	1		ENSP00000427589.1	P54107-1
CRISP1	ENST00000507853.5 link	c.362G>A	p.Ser121Asn	missense_variant	Exon 5 of 7	1		ENSP00000425020.1	P54107-2
CRISP1	ENST00000329411.9 link	c.362G>A	p.Ser121Asn	missense_variant	Exon 4 of 6	5		ENSP00000331317.5	P54107-2

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

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

GnomAD3 exomes

AF:

0.000251

AC:

AN:

251036

Hom.:

AF XY:

0.000228

AC XY:

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00177

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:

0.00000881

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000479

AC:

AN:

1461318

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000719

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

Alfa

AF:

0.0000432

Hom.:

Bravo

AF:

0.000155

ExAC

AF:

0.000255

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.62

DANN

Benign

0.36

DEOGEN2

Benign

0.030

.;T;.;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.54

.;.;T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.018

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.28

N;N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

1.1

N;N;N;N

REVEL

Benign

0.032

Sift

Benign

0.54

T;T;T;T

Sift4G

Benign

0.78

T;T;T;T

Polyphen

0.0010

B;B;B;B

Vest4

0.030

MVP

0.15

MPC

0.014

ClinPred

0.015

GERP RS

-0.15

Varity_R

0.038

gMVP

0.12

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