chr8-75016917-A-G

Position:

• chr8-75016917-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031461.6(CRISPLD1):​c.905A>G​(p.Gln302Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000707 in 1,414,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CRISPLD1 NM_031461.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.70

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30754453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRISPLD1	NM_031461.6	c.905A>G	p.Gln302Arg	missense_variant	8/15	ENST00000262207.9
CRISPLD1	NM_001286777.2	c.347A>G	p.Gln116Arg	missense_variant	6/13
CRISPLD1	NM_001286778.2	c.341A>G	p.Gln114Arg	missense_variant	7/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRISPLD1	ENST00000262207.9	c.905A>G	p.Gln302Arg	missense_variant	8/15	1	NM_031461.6	P1
CRISPLD1	ENST00000517786.1	c.347A>G	p.Gln116Arg	missense_variant	6/13	2
CRISPLD1	ENST00000523524.5	c.341A>G	p.Gln114Arg	missense_variant	7/14	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1414590 Hom.: 0 Cov.: 29 AF XY: 0.00000143 AC XY: 1 AN XY: 701450

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: 9.20e-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

Jun 04, 2024

The c.905A>G (p.Q302R) alteration is located in exon 8 (coding exon 7) of the CRISPLD1 gene. This alteration results from a A to G substitution at nucleotide position 905, causing the glutamine (Q) at amino acid position 302 to be replaced by an arginine (R). 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	0.083
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;.;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.0052
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	-0.10	N;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.19	N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.48	T;T;T
Sift4G	Benign	0.60	T;T;T
Polyphen		0.070	B;.;.
Vest4		0.41
MutPred		0.48		Gain of MoRF binding (P = 0.0271);.;.;
MVP		0.85
MPC		0.23
ClinPred		0.95	D
GERP RS		4.7
Varity_R		0.27
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-75929152;