8-75014899-T-A

Position:

• chr8-75014899-T-A

Variant summary

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

The NM_031461.6(CRISPLD1):​c.714T>A​(p.Asn238Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRISPLD1 NM_031461.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.590

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	Protein	UniProt
CRISPLD1	NM_031461.6	c.714T>A	p.Asn238Lys	missense_variant	6/15	ENST00000262207.9	NP_113649.1
CRISPLD1	NM_001286777.2	c.156T>A	p.Asn52Lys	missense_variant	4/13		NP_001273706.1
CRISPLD1	NM_001286778.2	c.150T>A	p.Asn50Lys	missense_variant	5/14		NP_001273707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRISPLD1	ENST00000262207.9	c.714T>A	p.Asn238Lys	missense_variant	6/15	1	NM_031461.6	ENSP00000262207.4
CRISPLD1	ENST00000517786.1	c.156T>A	p.Asn52Lys	missense_variant	4/13	2		ENSP00000429746.1
CRISPLD1	ENST00000523524.5	c.150T>A	p.Asn50Lys	missense_variant	5/14	2		ENSP00000430105.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Aug 20, 2024

The c.714T>A (p.N238K) alteration is located in exon 6 (coding exon 5) of the CRISPLD1 gene. This alteration results from a T to A substitution at nucleotide position 714, causing the asparagine (N) at amino acid position 238 to be replaced by a lysine (K). 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	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;.;.
Eigen	Benign	0.097
Eigen_PC	Benign	0.047
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Uncertain	2.5	M;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.4	D;D;D
REVEL	Uncertain	0.51
Sift	Benign	0.069	T;D;D
Sift4G	Uncertain	0.046	D;D;D
Polyphen		0.69	P;.;.
Vest4		0.87
MutPred		0.44		Gain of methylation at N238 (P = 0.0044);.;.;
MVP		0.93
MPC		0.25
ClinPred		0.99	D
GERP RS		1.1
Varity_R		0.42
gMVP		0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-75927134; COSMIC: COSV100081516; COSMIC: COSV100081516;