chr22-24302045-CA-C

Position:

• chr22-24302045-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015330.6(SPECC1L):​c.-37-135del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 411,172 control chromosomes in the GnomAD database, including 174 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (173 hom., cov: 31)
  • Exomes 𝑓: 0.15 (1 hom.)
• Consequence: SPECC1L NM_015330.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0460

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 -10 ACMG points.

• BP6: Variant 22-24302045-CA-C is Benign according to our data. Variant chr22-24302045-CA-C is described in ClinVar as [Benign]. Clinvar id is 1291907.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPECC1L	NM_015330.6	c.-37-135del		intron_variant		ENST00000314328.14
SPECC1L-ADORA2A	NR_103546.1	n.272-135del		intron_variant, non_coding_transcript_variant
SPECC1L	NM_001145468.4	c.-37-135del		intron_variant
SPECC1L	NM_001254732.3	c.-37-135del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPECC1L	ENST00000314328.14	c.-37-135del		intron_variant		1	NM_015330.6	P1

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 3801 AN: 128286 Hom.: 173 Cov.: 31

Gnomad AFR AF: 0.0984

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.000989

Gnomad EAS AF: 0.00112

Gnomad SAS AF: 0.000245

Gnomad FIN AF: 0.00650

Gnomad MID AF: 0.0346

Gnomad NFE AF: 0.00162

Gnomad OTH AF: 0.0220

GnomAD4 exome AF: 0.154 AC: 43590 AN: 282848 Hom.: 1 AF XY: 0.154 AC XY: 23241 AN XY: 151394

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.166

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.149

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.0297 AC: 3815 AN: 128324 Hom.: 173 Cov.: 31 AF XY: 0.0292 AC XY: 1791 AN XY: 61428

Gnomad4 AFR AF: 0.0986

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.000989

Gnomad4 EAS AF: 0.00112

Gnomad4 SAS AF: 0.000246

Gnomad4 FIN AF: 0.00650

Gnomad4 NFE AF: 0.00162

Gnomad4 OTH AF: 0.0218

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs759458885; hg19: chr22-24698013;