rs930231980

Variant names:

• chr11-66590917-T-A
• rs930231980
• NM_018219.3:c.2099A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-66590917-T-A
• chr11-66590917-T-C

Variant summary

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

The NM_018219.3(CCDC87):​c.2099A>T​(p.Asp700Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,461,222 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D700G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: CCDC87 NM_018219.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

Genes affected

CCDC87 (HGNC:25579): (coiled-coil domain containing 87) Predicted to be involved in positive regulation of acrosome reaction and positive regulation of fertilization. [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, 0.777

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC87	NM_018219.3	c.2099A>T	p.Asp700Val	missense_variant	Exon 1 of 1	ENST00000333861.5	NP_060689.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC87	ENST00000333861.5	c.2099A>T	p.Asp700Val	missense_variant	Exon 1 of 1	6	NM_018219.3	ENSP00000328487.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249766 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135276

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000226 AC: 33 AN: 1461222 Hom.: 0 Cov.: 35 AF XY: 0.0000234 AC XY: 17 AN XY: 726912

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: 0.0000288

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.96	D
Vest4		0.76
MutPred		0.53		Loss of disorder (P = 0.0361);
MVP		0.63
MPC		0.59
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.63
gMVP		0.71

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: rs930231980; hg19: chr11-66358388;