rs139166286
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_015330.6(SPECC1L):c.2886G>A(p.Ser962Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 1,611,170 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0014 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00013 ( 1 hom. )
Consequence
SPECC1L
NM_015330.6 synonymous
NM_015330.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.20
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 22-24365534-G-A is Benign according to our data. Variant chr22-24365534-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 436843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.2 with no splicing effect.
BS2
High AC in GnomAd4 at 220 AD gene.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPECC1L | ENST00000314328.14 | c.2886G>A | p.Ser962Ser | synonymous_variant | Exon 13 of 17 | 1 | NM_015330.6 | ENSP00000325785.8 | ||
SPECC1L-ADORA2A | ENST00000358654.2 | n.*272G>A | non_coding_transcript_exon_variant | Exon 14 of 20 | 2 | ENSP00000351480.2 | ||||
SPECC1L-ADORA2A | ENST00000358654.2 | n.*272G>A | 3_prime_UTR_variant | Exon 14 of 20 | 2 | ENSP00000351480.2 |
Frequencies
GnomAD3 genomes AF: 0.00139 AC: 212AN: 152074Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
212
AN:
152074
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000371 AC: 90AN: 242442Hom.: 1 AF XY: 0.000326 AC XY: 43AN XY: 132074
GnomAD3 exomes
AF:
AC:
90
AN:
242442
Hom.:
AF XY:
AC XY:
43
AN XY:
132074
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000127 AC: 186AN: 1458980Hom.: 1 Cov.: 34 AF XY: 0.000109 AC XY: 79AN XY: 725750
GnomAD4 exome
AF:
AC:
186
AN:
1458980
Hom.:
Cov.:
34
AF XY:
AC XY:
79
AN XY:
725750
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00145 AC: 220AN: 152190Hom.: 0 Cov.: 31 AF XY: 0.00156 AC XY: 116AN XY: 74406
GnomAD4 genome
AF:
AC:
220
AN:
152190
Hom.:
Cov.:
31
AF XY:
AC XY:
116
AN XY:
74406
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | SPECC1L: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 12, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 05, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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