chr22-24302362-G-C

Variant names:

• chr22-24302362-G-C
• NM_015330.6:c.131G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015330.6(SPECC1L):​c.131G>C​(p.Gly44Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SPECC1L NM_015330.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.53

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07500669).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPECC1L	NM_015330.6	c.131G>C	p.Gly44Ala	missense_variant	Exon 3 of 17	ENST00000314328.14	NP_056145.5
SPECC1L	NM_001145468.4	c.131G>C	p.Gly44Ala	missense_variant	Exon 2 of 16		NP_001138940.4
SPECC1L	NM_001254732.3	c.131G>C	p.Gly44Ala	missense_variant	Exon 2 of 15		NP_001241661.3
SPECC1L-ADORA2A	NR_103546.1	n.439G>C		non_coding_transcript_exon_variant	Exon 3 of 20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPECC1L	ENST00000314328.14	c.131G>C	p.Gly44Ala	missense_variant	Exon 3 of 17	1	NM_015330.6	ENSP00000325785.8
SPECC1L-ADORA2A	ENST00000358654.2	n.131G>C		non_coding_transcript_exon_variant	Exon 3 of 20	2		ENSP00000351480.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461826 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727210

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Uncertain	0.99
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.79	.;T;.;.
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.075	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.040	N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.45	T;T;T;T
Sift4G	Benign	0.78	T;T;T;T
Vest4		0.31
MutPred		0.059		Loss of methylation at K39 (P = 0.1246);Loss of methylation at K39 (P = 0.1246);Loss of methylation at K39 (P = 0.1246);Loss of methylation at K39 (P = 0.1246);
MVP		0.57
MPC		0.47
ClinPred		0.45	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.077

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-24698330;