8-75017344-A-G

Position:

• chr8-75017344-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031461.6(CRISPLD1):​c.1021A>G​(p.Ile341Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,456,384 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CRISPLD1 NM_031461.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.55

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRISPLD1	NM_031461.6	c.1021A>G	p.Ile341Val	missense_variant	10/15	ENST00000262207.9
CRISPLD1	NM_001286777.2	c.463A>G	p.Ile155Val	missense_variant	8/13
CRISPLD1	NM_001286778.2	c.457A>G	p.Ile153Val	missense_variant	9/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRISPLD1	ENST00000262207.9	c.1021A>G	p.Ile341Val	missense_variant	10/15	1	NM_031461.6	P1
CRISPLD1	ENST00000517786.1	c.463A>G	p.Ile155Val	missense_variant	8/13	2
CRISPLD1	ENST00000523524.5	c.457A>G	p.Ile153Val	missense_variant	9/14	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1456384 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 724184

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: 0.0000237

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.1021A>G (p.I341V) alteration is located in exon 10 (coding exon 9) of the CRISPLD1 gene. This alteration results from a A to G substitution at nucleotide position 1021, causing the isoleucine (I) at amino acid position 341 to be replaced by a valine (V). 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	0.082
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Uncertain	0.11	D
MutationAssessor	Uncertain	2.0	M;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.55	N;N;N
REVEL	Uncertain	0.41
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.27	B;.;.
Vest4		0.46
MutPred		0.69		Gain of catalytic residue at I341 (P = 0.0285);.;.;
MVP		0.69
MPC		0.33
ClinPred		0.59	D
GERP RS		4.3
Varity_R		0.038
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs1813051006; hg19: chr8-75929579;