rs12051468

Variant names:

• chr16-84845858-A-C
• NM_031476.4:c.313A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-84845858-A-C
• chr16-84845858-A-G
• chr16-84845858-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031476.4(CRISPLD2):​c.313A>C​(p.Ser105Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S105G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CRISPLD2 NM_031476.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414

Genes affected

CRISPLD2 (HGNC:25248): (cysteine rich secretory protein LCCL domain containing 2) Predicted to enable glycosaminoglycan binding activity. Involved in face morphogenesis. Located in transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285848 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06020382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRISPLD2	NM_031476.4	c.313A>C	p.Ser105Arg	missense_variant	Exon 3 of 15	ENST00000262424.10	NP_113664.1
CRISPLD2	XM_005256190.2	c.313A>C	p.Ser105Arg	missense_variant	Exon 4 of 16		XP_005256247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRISPLD2	ENST00000262424.10	c.313A>C	p.Ser105Arg	missense_variant	Exon 3 of 15	1	NM_031476.4	ENSP00000262424.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461530 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 727060

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: 8.99e-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	Uncertain	0.36
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.3
DANN	Benign	0.87
DEOGEN2	Benign	0.0052	T;T;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.056	N
LIST_S2	Uncertain	0.88	D;D;D;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.060	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.61	N;.;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.083
Sift	Benign	0.33	T;T;T;T
Sift4G	Benign	0.55	T;T;T;T
Polyphen		0.0	B;.;B;P
Vest4		0.25
MutPred		0.47		Gain of MoRF binding (P = 0.028);Gain of MoRF binding (P = 0.028);Gain of MoRF binding (P = 0.028);Gain of MoRF binding (P = 0.028);
MVP		0.21
MPC		0.13
ClinPred		0.092	T
GERP RS		-5.8
Varity_R		0.090
gMVP		0.59

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: chr16-84879464;