NM_015330.6:c.2886G>A

Variant summary

Our verdict is Benign. The variant received -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

Publications

2 publications found
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 was made for transcript

Our verdict: Benign. The variant received -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
GnomAD2 exomes
AF:
0.000371
AC:
90
AN:
242442
AF XY:
0.000326
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 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
African (AFR)
AF:
0.00439
AC:
147
AN:
33454
American (AMR)
AF:
0.000383
AC:
17
AN:
44440
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26020
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39606
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86104
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52178
Middle Eastern (MID)
AF:
0.000524
AC:
3
AN:
5724
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1111242
Other (OTH)
AF:
0.000266
AC:
16
AN:
60212
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.464
Heterozygous variant carriers
0
10
21
31
42
52
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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
African (AFR)
AF:
0.00506
AC:
210
AN:
41528
American (AMR)
AF:
0.000458
AC:
7
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5168
South Asian (SAS)
AF:
0.000208
AC:
1
AN:
4818
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10596
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68006
Other (OTH)
AF:
0.000948
AC:
2
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
13
26
40
53
66
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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
Jun 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

SPECC1L: BP4, BP7 -

Aug 12, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not specified Benign:1
Jan 05, 2017
Genetic Services Laboratory, University of Chicago
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
0.32
DANN
Benign
0.82
PhyloP100
-1.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs139166286; hg19: chr22-24761502; API