chr22-24302045-C-CAA

Variant names:

• chr22-24302045-C-CAA
• rs759458885
• NM_015330.6:c.-37-136_-37-135dupAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_015330.6(SPECC1L):​c.-37-136_-37-135dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 462,926 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000016 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (0 hom.)
• Consequence: SPECC1L NM_015330.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 566 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPECC1L	NM_015330.6	c.-37-136_-37-135dupAA		intron_variant	Intron 2 of 16	ENST00000314328.14	NP_056145.5
SPECC1L	NM_001145468.4	c.-37-136_-37-135dupAA		intron_variant	Intron 1 of 15		NP_001138940.4
SPECC1L	NM_001254732.3	c.-37-136_-37-135dupAA		intron_variant	Intron 1 of 14		NP_001241661.3
SPECC1L-ADORA2A	NR_103546.1	n.272-136_272-135dupAA		intron_variant	Intron 2 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPECC1L	ENST00000314328.14	c.-37-150_-37-149insAA		intron_variant	Intron 2 of 16	1	NM_015330.6	ENSP00000325785.8
SPECC1L-ADORA2A	ENST00000358654.2	n.-37-150_-37-149insAA		intron_variant	Intron 2 of 19	2		ENSP00000351480.2

Frequencies

GnomAD3 genomes AF: 0.0000156 AC: 2 AN: 128508 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000143

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000168

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00169 AC: 566 AN: 334418 Hom.: 0 AF XY: 0.00164 AC XY: 294 AN XY: 179804

Gnomad4 AFR exome AF: 0.00135

Gnomad4 AMR exome AF: 0.000926

Gnomad4 ASJ exome AF: 0.00308

Gnomad4 EAS exome AF: 0.00197

Gnomad4 SAS exome AF: 0.000358

Gnomad4 FIN exome AF: 0.00158

Gnomad4 NFE exome AF: 0.00190

Gnomad4 OTH exome AF: 0.00219

GnomAD4 genome AF: 0.0000156 AC: 2 AN: 128508 Hom.: 0 Cov.: 31 AF XY: 0.0000163 AC XY: 1 AN XY: 61506

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000143

Gnomad4 NFE AF: 0.0000168

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs759458885; hg19: chr22-24698013;