rs17004911

chr22-24397271-C-Gchr22-24397271-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015330.6(SPECC1L):c.3088-14317C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 152,204 control chromosomes in the GnomAD database, including 177 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 0.034 (177 hom., cov: 32)
• Consequence: SPECC1L NM_015330.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.492

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPECC1L	NM_015330.6	c.3088-14317C>G		intron_variant		ENST00000314328.14
SPECC1L-ADORA2A	NR_103546.1	n.3518-14317C>G		intron_variant, non_coding_transcript_variant
LOC105372960	XR_938082.3	n.136-2935G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPECC1L	ENST00000314328.14	c.3088-14317C>G		intron_variant		1	NM_015330.6	P1
SPECC1L	ENST00000437398.5	c.3088-14317C>G		intron_variant		1		P1
SPECC1L	ENST00000541492.1	c.3088-15377C>G		intron_variant		2
SPECC1L	ENST00000651059.1	c.3145-14317C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0335 AC: 5093 AN: 152086 Hom.: 175 Cov.: 32

Gnomad AFR AF: 0.0818

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00436

Gnomad FIN AF: 0.00792

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0141

Gnomad OTH AF: 0.0278

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

GnomAD4 genome AF: 0.0336 AC: 5117 AN: 152204 Hom.: 177 Cov.: 32 AF XY: 0.0326 AC XY: 2424 AN XY: 74412

Gnomad4 AFR AF: 0.0821

Gnomad4 AMR AF: 0.0315

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00436

Gnomad4 FIN AF: 0.00792

Gnomad4 NFE AF: 0.0141

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.00772 Hom.: 5

Bravo AF: 0.0369

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	15
Dann	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs17004911; hg19: chr22-24793239;