22-24321542-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_015330.6(SPECC1L):c.562C>T(p.Leu188Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00654 in 1,614,182 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0074 ( 10 hom., cov: 33)
Exomes 𝑓: 0.0064 ( 61 hom. )
Consequence
SPECC1L
NM_015330.6 missense
NM_015330.6 missense
Scores
7
4
5
Clinical Significance
Conservation
PhyloP100: 3.34
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]
SPECC1L-ADORA2A (HGNC:49185): (SPECC1L-ADORA2A readthrough (NMD candidate)) This locus represents naturally occurring readthrough transcription between the neighboring SPECC1L (sperm antigen with calponin homology and coiled-coil domains 1-like) and ADORA2A (adenosine A2a receptor) genes on chromosome 22. The readthrough transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Jun 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0059348345).
BP6
Variant 22-24321542-C-T is Benign according to our data. Variant chr22-24321542-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-24321542-C-T is described in Lovd as [Likely_benign].
BS2
High AC in GnomAd4 at 1134 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPECC1L | NM_015330.6 | c.562C>T | p.Leu188Phe | missense_variant | Exon 5 of 17 | ENST00000314328.14 | NP_056145.5 | |
SPECC1L | NM_001145468.4 | c.562C>T | p.Leu188Phe | missense_variant | Exon 4 of 16 | NP_001138940.4 | ||
SPECC1L | NM_001254732.3 | c.562C>T | p.Leu188Phe | missense_variant | Exon 4 of 15 | NP_001241661.3 | ||
SPECC1L-ADORA2A | NR_103546.1 | n.870C>T | non_coding_transcript_exon_variant | Exon 5 of 20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPECC1L | ENST00000314328.14 | c.562C>T | p.Leu188Phe | missense_variant | Exon 5 of 17 | 1 | NM_015330.6 | ENSP00000325785.8 | ||
SPECC1L-ADORA2A | ENST00000358654.2 | n.562C>T | non_coding_transcript_exon_variant | Exon 5 of 20 | 2 | ENSP00000351480.2 |
Frequencies
GnomAD3 genomes AF: 0.00745 AC: 1134AN: 152204Hom.: 10 Cov.: 33
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GnomAD3 exomes AF: 0.00767 AC: 1930AN: 251468Hom.: 17 AF XY: 0.00781 AC XY: 1061AN XY: 135912
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GnomAD4 exome AF: 0.00644 AC: 9415AN: 1461860Hom.: 61 Cov.: 32 AF XY: 0.00642 AC XY: 4667AN XY: 727238
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GnomAD4 genome AF: 0.00744 AC: 1134AN: 152322Hom.: 10 Cov.: 33 AF XY: 0.00836 AC XY: 623AN XY: 74490
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 03, 2025 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2024 | SPECC1L: BS2 - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 29, 2017 | - - |
Oculomaxillofacial dysostosis;CN306405:Teebi hypertelorism syndrome 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 25, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
.;D;.;.;D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;D
REVEL
Benign
Sift
Pathogenic
D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D
Vest4
MVP
MPC
1.3
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at