rs757499695

Variant names:

• chr8-74986036-A-C
• rs757499695
• NM_031461.6:c.49A>C

Your query was ambiguous. Multiple possible variants found:

• chr8-74986036-A-C
• chr8-74986036-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031461.6(CRISPLD1):​c.49A>C​(p.Met17Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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: Not reported in ClinVar
• Conservation: PhyloP100: 0.971

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.097631246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRISPLD1	NM_031461.6	c.49A>C	p.Met17Leu	missense_variant	Exon 2 of 15	ENST00000262207.9	NP_113649.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRISPLD1	ENST00000262207.9	c.49A>C	p.Met17Leu	missense_variant	Exon 2 of 15	1	NM_031461.6	ENSP00000262207.4
CRISPLD1	ENST00000520277.1	c.49A>C	p.Met17Leu	missense_variant	Exon 3 of 4	5		ENSP00000430504.1
CRISPLD1	ENST00000519798.1	n.430A>C		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.72
DEOGEN2	Benign	0.022	T;.
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.098	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.41	N;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.51	N;N
REVEL	Benign	0.026
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.19
MutPred		0.67		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP		0.55
MPC		0.18
ClinPred		0.032	T
GERP RS		3.0
Varity_R		0.075
gMVP		0.36

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

LitVar

Other links and lift over

dbSNP: rs757499695; hg19: chr8-75898271;