NM_015330.6:c.570G>A

Variant names:

• chr22-24321550-G-A
• rs3747113
• NM_015330.6:c.570G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015330.6(SPECC1L):​c.570G>A​(p.Thr190Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,613,942 control chromosomes in the GnomAD database, including 53,073 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4154 hom., cov: 33)
  • Exomes 𝑓: 0.26 (48919 hom.)
• Consequence: SPECC1L NM_015330.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -3.42
• Publications: 22 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]

ENSG00000299949 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 22-24321550-G-A is Benign according to our data. Variant chr22-24321550-G-A is described in ClinVar as Benign. ClinVar VariationId is 1282641.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.42 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPECC1L	NM_015330.6	c.570G>A	p.Thr190Thr	synonymous_variant	Exon 5 of 17	ENST00000314328.14	NP_056145.5
SPECC1L	NM_001145468.4	c.570G>A	p.Thr190Thr	synonymous_variant	Exon 4 of 16		NP_001138940.4
SPECC1L	NM_001254732.3	c.570G>A	p.Thr190Thr	synonymous_variant	Exon 4 of 15		NP_001241661.3
SPECC1L-ADORA2A	NR_103546.1	n.878G>A		non_coding_transcript_exon_variant	Exon 5 of 20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPECC1L	ENST00000314328.14	c.570G>A	p.Thr190Thr	synonymous_variant	Exon 5 of 17	1	NM_015330.6	ENSP00000325785.8
SPECC1L-ADORA2A	ENST00000358654.2	n.570G>A		non_coding_transcript_exon_variant	Exon 5 of 20	2		ENSP00000351480.2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34189 AN: 152028 Hom.: 4150 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.233

GnomAD2 exomes AF: 0.245 AC: 61636 AN: 251396 AF XY: 0.242

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.324

Gnomad ASJ exome AF: 0.234

Gnomad EAS exome AF: 0.226

Gnomad FIN exome AF: 0.243

Gnomad NFE exome AF: 0.258

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.256 AC: 374357 AN: 1461796 Hom.: 48919 Cov.: 38 AF XY: 0.253 AC XY: 184208 AN XY: 727210

African (AFR) AF: 0.136 AC: 4563 AN: 33480

American (AMR) AF: 0.327 AC: 14604 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 6215 AN: 26136

East Asian (EAS) AF: 0.268 AC: 10621 AN: 39700

South Asian (SAS) AF: 0.181 AC: 15592 AN: 86256

European-Finnish (FIN) AF: 0.243 AC: 12974 AN: 53368

Middle Eastern (MID) AF: 0.245 AC: 1412 AN: 5768

European-Non Finnish (NFE) AF: 0.264 AC: 293301 AN: 1111972

Other (OTH) AF: 0.250 AC: 15075 AN: 60394

GnomAD4 genome AF: 0.225 AC: 34219 AN: 152146 Hom.: 4154 Cov.: 33 AF XY: 0.226 AC XY: 16777 AN XY: 74382

African (AFR) AF: 0.137 AC: 5681 AN: 41516

American (AMR) AF: 0.291 AC: 4443 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 808 AN: 3468

East Asian (EAS) AF: 0.232 AC: 1202 AN: 5180

South Asian (SAS) AF: 0.172 AC: 830 AN: 4814

European-Finnish (FIN) AF: 0.252 AC: 2669 AN: 10578

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17869 AN: 67984

Other (OTH) AF: 0.237 AC: 501 AN: 2114

Alfa AF: 0.250 Hom.: 9097

Bravo AF: 0.226

Asia WGS AF: 0.222 AC: 773 AN: 3478

EpiCase AF: 0.260

EpiControl AF: 0.260

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 12, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Teebi hypertelorism syndrome Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant Opitz G/BBB syndrome Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oculomaxillofacial dysostosis Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.38
DANN	Benign	0.64
PhyloP100		-3.4
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: rs3747113; hg19: chr22-24717518; COSMIC: COSV58657272;