Genetic Variant SPECC1L:c.-37-136_-37-135dupAA (chr22-24302045-C-CAA) – ACMG Classification: Likely_benign (-4 pts)

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0460

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 links:

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]

SPECC1L-ADORA2A links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 566 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SPECC1L	NM_015330.6 link	c.-37-136_-37-135dupAA	intron_variant	Intron 2 of 16	ENST00000314328.14	NP_056145.5	Q69YQ0-1B2RMV2
SPECC1L	NM_001145468.4 link	c.-37-136_-37-135dupAA	intron_variant	Intron 1 of 15		NP_001138940.4	B2RMV2
SPECC1L	NM_001254732.3 link	c.-37-136_-37-135dupAA	intron_variant	Intron 1 of 14		NP_001241661.3	Q69YQ0-2
SPECC1L-ADORA2A	NR_103546.1 link	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 link	c.-37-150_-37-149insAA		intron_variant	Intron 2 of 16	1	NM_015330.6	ENSP00000325785.8		Q69YQ0-1
SPECC1L-ADORA2A	ENST00000358654.2 link	n.-37-150_-37-149insAA		intron_variant	Intron 2 of 19	2		ENSP00000351480.2		F8WAN1

Frequencies

GnomAD3 genomes

AF:

0.0000156

AC:

AN:

128508

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00164

AC XY:

294

AN XY:

179804

show subpopulations

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:

AN:

128508

Hom.:

Cov.:

AF XY:

0.0000163

AC XY:

AN XY:

61506

show subpopulations

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

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

22-24302045-CAAAAAA-CAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over