rs139166286

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

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.20
Variant links:
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

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPECC1LNM_015330.6 linkc.2886G>A p.Ser962Ser synonymous_variant Exon 13 of 17 ENST00000314328.14 NP_056145.5 Q69YQ0-1B2RMV2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPECC1LENST00000314328.14 linkc.2886G>A p.Ser962Ser synonymous_variant Exon 13 of 17 1 NM_015330.6 ENSP00000325785.8 Q69YQ0-1
SPECC1L-ADORA2AENST00000358654.2 linkn.*272G>A non_coding_transcript_exon_variant Exon 14 of 20 2 ENSP00000351480.2 F8WAN1
SPECC1L-ADORA2AENST00000358654.2 linkn.*272G>A 3_prime_UTR_variant Exon 14 of 20 2 ENSP00000351480.2 F8WAN1

Frequencies

GnomAD3 genomes
AF:
0.00139
AC:
212
AN:
152074
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00488
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000958
GnomAD3 exomes
AF:
0.000371
AC:
90
AN:
242442
Hom.:
1
AF XY:
0.000326
AC XY:
43
AN XY:
132074
show subpopulations
Gnomad AFR exome
AF:
0.00542
Gnomad AMR exome
AF:
0.000295
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000127
AC:
186
AN:
1458980
Hom.:
1
Cov.:
34
AF XY:
0.000109
AC XY:
79
AN XY:
725750
show subpopulations
Gnomad4 AFR exome
AF:
0.00439
Gnomad4 AMR exome
AF:
0.000383
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.000266
GnomAD4 genome
AF:
0.00145
AC:
220
AN:
152190
Hom.:
0
Cov.:
31
AF XY:
0.00156
AC XY:
116
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.00506
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000948
Alfa
AF:
0.00120
Hom.:
0
Bravo
AF:
0.00159

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 submitterclinical testingCeGaT Center for Human Genetics TuebingenJun 01, 2023SPECC1L: BP4, BP7 -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 12, 2024- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoJan 05, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
0.32
DANN
Benign
0.82
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs139166286; hg19: chr22-24761502; API