22-24406596-G-A

Variant names:

• chr22-24406596-G-A
• rs5751862
• NM_015330.6:c.3088-4992G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015330.6(SPECC1L):​c.3088-4992G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,956 control chromosomes in the GnomAD database, including 13,137 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (13137 hom., cov: 31)
• Consequence: SPECC1L NM_015330.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.20
• Publications: 21 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPECC1L	NM_015330.6	MANE Select	c.3088-4992G>A		intron	N/A	NP_056145.5
	SPECC1L	NM_001145468.4		c.3088-4992G>A		intron	N/A	NP_001138940.4
	SPECC1L	NM_001254732.3		c.3088-6052G>A		intron	N/A	NP_001241661.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPECC1L	ENST00000314328.14	TSL:1 MANE Select	c.3088-4992G>A		intron	N/A	ENSP00000325785.8
	SPECC1L	ENST00000437398.5	TSL:1	c.3088-4992G>A		intron	N/A	ENSP00000393363.1
	SPECC1L-ADORA2A	ENST00000358654.2	TSL:2	n.*474-4992G>A		intron	N/A	ENSP00000351480.2

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60331 AN: 151838 Hom.: 13117 Cov.: 31

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.388

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.420

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.397 AC: 60380 AN: 151956 Hom.: 13137 Cov.: 31 AF XY: 0.398 AC XY: 29582 AN XY: 74256

African (AFR) AF: 0.213 AC: 8838 AN: 41454

American (AMR) AF: 0.462 AC: 7058 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1523 AN: 3468

East Asian (EAS) AF: 0.466 AC: 2400 AN: 5146

South Asian (SAS) AF: 0.294 AC: 1417 AN: 4814

European-Finnish (FIN) AF: 0.486 AC: 5135 AN: 10556

Middle Eastern (MID) AF: 0.383 AC: 111 AN: 290

European-Non Finnish (NFE) AF: 0.480 AC: 32635 AN: 67934

Other (OTH) AF: 0.421 AC: 891 AN: 2114

Alfa AF: 0.454 Hom.: 66794

Bravo AF: 0.394

Asia WGS AF: 0.376 AC: 1306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.46
PhyloP100		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5751862; hg19: chr22-24802564;