rs1167817081

Variant names:

• chr8-75013999-A-C
• NM_031461.6:c.523A>C

Your query was ambiguous. Multiple possible variants found:

• chr8-75013999-A-C
• chr8-75013999-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_031461.6(CRISPLD1):​c.523A>C​(p.Thr175Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CRISPLD1 NM_031461.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.20

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.784

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRISPLD1	NM_031461.6	c.523A>C	p.Thr175Pro	missense_variant	Exon 5 of 15	ENST00000262207.9	NP_113649.1
CRISPLD1	NM_001286778.2	c.-42A>C		5_prime_UTR_variant	Exon 4 of 14		NP_001273707.1
CRISPLD1	NM_001286777.2	c.69-813A>C		intron_variant	Intron 3 of 12		NP_001273706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRISPLD1	ENST00000262207.9	c.523A>C	p.Thr175Pro	missense_variant	Exon 5 of 15	1	NM_031461.6	ENSP00000262207.4
CRISPLD1	ENST00000523524	c.-42A>C		5_prime_UTR_variant	Exon 4 of 14	2		ENSP00000430105.1
CRISPLD1	ENST00000517786.1	c.69-813A>C		intron_variant	Intron 3 of 12	2		ENSP00000429746.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460210 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726456

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.50		Gain of sheet (P = 0.0827);
MVP		0.87
MPC		0.85
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.84
gMVP		0.87

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: chr8-75926234;