22-24302045-CAAAAAA-C

Variant names:

• chr22-24302045-CAAAAAA-C
• rs759458885
• NM_015330.6:c.-37-140_-37-135delAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015330.6(SPECC1L):​c.-37-140_-37-135delAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000297 in 336,648 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: SPECC1L NM_015330.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015330.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPECC1L	NM_015330.6	MANE Select	c.-37-140_-37-135delAAAAAA		intron	N/A	NP_056145.5	Q69YQ0-1
	SPECC1L	NM_001145468.4		c.-37-140_-37-135delAAAAAA		intron	N/A	NP_001138940.4	Q69YQ0-1
	SPECC1L	NM_001254732.3		c.-37-140_-37-135delAAAAAA		intron	N/A	NP_001241661.3	Q69YQ0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPECC1L	ENST00000314328.14	TSL:1 MANE Select	c.-37-149_-37-144delAAAAAA		intron	N/A	ENSP00000325785.8	Q69YQ0-1
	SPECC1L	ENST00000437398.5	TSL:1	c.-37-149_-37-144delAAAAAA		intron	N/A	ENSP00000393363.1	Q69YQ0-1
	SPECC1L-ADORA2A	ENST00000358654.2	TSL:2	n.-37-149_-37-144delAAAAAA		intron	N/A	ENSP00000351480.2	F8WAN1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000297 AC: 1 AN: 336648 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 180990

African (AFR) AF: 0.00 AC: 0 AN: 8922

American (AMR) AF: 0.00 AC: 0 AN: 14120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9466

East Asian (EAS) AF: 0.00 AC: 0 AN: 18978

South Asian (SAS) AF: 0.00 AC: 0 AN: 39202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17884

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1338

European-Non Finnish (NFE) AF: 0.00000479 AC: 1 AN: 208796

Other (OTH) AF: 0.00 AC: 0 AN: 17942

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

Splicing

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

Other links and lift over

dbSNP: rs759458885; hg19: chr22-24698013;