8-75014083-G-A

Variant names:

• chr8-75014083-G-A
• NM_031461.6:c.607G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_031461.6(CRISPLD1):​c.607G>A​(p.Val203Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 9.87
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.869

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.607G>A	p.Val203Met	missense	Exon 5 of 15	NP_113649.1	Q9H336-1
	CRISPLD1	NM_001286778.2		c.43G>A	p.Val15Met	missense	Exon 4 of 14	NP_001273707.1	B7Z8V9
	CRISPLD1	NM_001286777.2		c.69-729G>A		intron	N/A	NP_001273706.1	Q9H336-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRISPLD1	ENST00000262207.9	TSL:1 MANE Select	c.607G>A	p.Val203Met	missense	Exon 5 of 15	ENSP00000262207.4	Q9H336-1
	CRISPLD1	ENST00000959492.1		c.607G>A	p.Val203Met	missense	Exon 5 of 15	ENSP00000629551.1
	CRISPLD1	ENST00000916000.1		c.607G>A	p.Val203Met	missense	Exon 5 of 15	ENSP00000586059.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

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	0.98
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.97
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.35	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Pathogenic	0.98	D
MutationAssessor	Pathogenic	4.5	H
PhyloP100		9.9
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.64		Loss of sheet (P = 0.0817)
MVP		0.84
MPC		0.62
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.50
gMVP		0.87
Mutation Taster		=20/80	disease causing

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: chr8-75926318;