rs1556226291
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP2PP5_Moderate
The NM_015330.6(SPECC1L):c.1292T>C(p.Leu431Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
SPECC1L
NM_015330.6 missense
NM_015330.6 missense
Scores
7
7
2
Clinical Significance
Conservation
PhyloP100: 7.84
Genes affected
SPECC1L (HGNC:29022): (sperm antigen with calponin homology and coiled-coil domains 1 like) This gene encodes a coiled-coil domain containing protein. The encoded protein may play a critical role in actin-cytoskeletal reorganization during facial morphogenesis. Mutations in this gene are a cause of oblique facial clefting-1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. A read-through transcript composed of SPECC1L (sperm antigen with calponin homology and coiled-coil domains 1-like) and the downstream ADORA2A (adenosine A2a receptor) gene sequence has been identified, but it is thought to be non-coding. [provided by RefSeq, Jun 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM1
?
In a coiled_coil_region (size 55) in uniprot entity CYTSA_HUMAN there are 13 pathogenic changes around while only 0 benign (100%) in NM_015330.6
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, SPECC1L
PP5
?
Variant 22-24322272-T-C is Pathogenic according to our data. Variant chr22-24322272-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 559898.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPECC1L | NM_015330.6 | c.1292T>C | p.Leu431Pro | missense_variant | 5/17 | ENST00000314328.14 | |
SPECC1L-ADORA2A | NR_103546.1 | n.1600T>C | non_coding_transcript_exon_variant | 5/20 | |||
SPECC1L | NM_001145468.4 | c.1292T>C | p.Leu431Pro | missense_variant | 4/16 | ||
SPECC1L | NM_001254732.3 | c.1292T>C | p.Leu431Pro | missense_variant | 4/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPECC1L | ENST00000314328.14 | c.1292T>C | p.Leu431Pro | missense_variant | 5/17 | 1 | NM_015330.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal dominant Opitz G/BBB syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | Aug 03, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Vest4
MutPred
Gain of glycosylation at L431 (P = 0.0334);Gain of glycosylation at L431 (P = 0.0334);Gain of glycosylation at L431 (P = 0.0334);Gain of glycosylation at L431 (P = 0.0334);
MVP
MPC
1.6
ClinPred
D
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at