22-24313323-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_015330.6(SPECC1L):c.164G>T(p.Ser55Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
SPECC1L
NM_015330.6 missense
NM_015330.6 missense
Scores
6
10
Clinical Significance
Conservation
PhyloP100: 0.352
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, SPECC1L
BP4
?
Computational evidence support a benign effect (MetaRNN=0.13630638).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPECC1L | NM_015330.6 | c.164G>T | p.Ser55Ile | missense_variant | 4/17 | ENST00000314328.14 | |
SPECC1L-ADORA2A | NR_103546.1 | n.472G>T | non_coding_transcript_exon_variant | 4/20 | |||
SPECC1L | NM_001145468.4 | c.164G>T | p.Ser55Ile | missense_variant | 3/16 | ||
SPECC1L | NM_001254732.3 | c.164G>T | p.Ser55Ile | missense_variant | 3/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPECC1L | ENST00000314328.14 | c.164G>T | p.Ser55Ile | missense_variant | 4/17 | 1 | NM_015330.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251452Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135904
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461862Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727234
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GnomAD4 genome ? Cov.: 32
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Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2022 | The c.164G>T (p.S55I) alteration is located in exon 4 (coding exon 2) of the SPECC1L gene. This alteration results from a G to T substitution at nucleotide position 164, causing the serine (S) at amino acid position 55 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;D;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Vest4
MutPred
Gain of loop (P = 0.0111);Gain of loop (P = 0.0111);Gain of loop (P = 0.0111);Gain of loop (P = 0.0111);
MVP
MPC
0.58
ClinPred
D
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