chr8-75014899-T-A

Variant names:

• chr8-75014899-T-A
• NM_031461.6:c.714T>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031461.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRISPLD1	NM_031461.6	MANE Select	c.714T>A	p.Asn238Lys	missense	Exon 6 of 15	NP_113649.1	Q9H336-1
	CRISPLD1	NM_001286777.2		c.156T>A	p.Asn52Lys	missense	Exon 4 of 13	NP_001273706.1	Q9H336-2
	CRISPLD1	NM_001286778.2		c.150T>A	p.Asn50Lys	missense	Exon 5 of 14	NP_001273707.1	B7Z8V9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRISPLD1	ENST00000262207.9	TSL:1 MANE Select	c.714T>A	p.Asn238Lys	missense	Exon 6 of 15	ENSP00000262207.4	Q9H336-1
	CRISPLD1	ENST00000959492.1		c.714T>A	p.Asn238Lys	missense	Exon 6 of 15	ENSP00000629551.1
	CRISPLD1	ENST00000916000.1		c.714T>A	p.Asn238Lys	missense	Exon 6 of 15	ENSP00000586059.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.59
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.51
Sift	Benign	0.069	T
Sift4G	Uncertain	0.046	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
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

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