chr22-24302061-T-A

Position:

• chr22-24302061-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015330.6(SPECC1L):​c.-37-134T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 614,716 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (142 hom., cov: 32)
  • Exomes 𝑓: 0.015 (31 hom.)
• Consequence: SPECC1L NM_015330.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.460

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 22-24302061-T-A is Benign according to our data. Variant chr22-24302061-T-A is described in ClinVar as [Benign]. Clinvar id is 1239666.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPECC1L	NM_015330.6	c.-37-134T>A		intron_variant		ENST00000314328.14
SPECC1L-ADORA2A	NR_103546.1	n.272-134T>A		intron_variant, non_coding_transcript_variant
SPECC1L	NM_001145468.4	c.-37-134T>A		intron_variant
SPECC1L	NM_001254732.3	c.-37-134T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPECC1L	ENST00000314328.14	c.-37-134T>A		intron_variant		1	NM_015330.6	P1

Frequencies

GnomAD3 genomes AF: 0.0314 AC: 4722 AN: 150448 Hom.: 140 Cov.: 32

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0281

Gnomad ASJ AF: 0.0289

Gnomad EAS AF: 0.00233

Gnomad SAS AF: 0.00590

Gnomad FIN AF: 0.00809

Gnomad MID AF: 0.0227

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.0252

GnomAD4 exome AF: 0.0148 AC: 6848 AN: 464150 Hom.: 31 AF XY: 0.0141 AC XY: 3460 AN XY: 245874

Gnomad4 AFR exome AF: 0.0738

Gnomad4 AMR exome AF: 0.0198

Gnomad4 ASJ exome AF: 0.0318

Gnomad4 EAS exome AF: 0.00442

Gnomad4 SAS exome AF: 0.00671

Gnomad4 FIN exome AF: 0.00685

Gnomad4 NFE exome AF: 0.0141

Gnomad4 OTH exome AF: 0.0183

GnomAD4 genome AF: 0.0315 AC: 4748 AN: 150566 Hom.: 142 Cov.: 32 AF XY: 0.0308 AC XY: 2267 AN XY: 73560

Gnomad4 AFR AF: 0.0750

Gnomad4 AMR AF: 0.0280

Gnomad4 ASJ AF: 0.0289

Gnomad4 EAS AF: 0.00233

Gnomad4 SAS AF: 0.00590

Gnomad4 FIN AF: 0.00809

Gnomad4 NFE AF: 0.0145

Gnomad4 OTH AF: 0.0269

Alfa AF: 0.0234 Hom.: 12

Bravo AF: 0.0338

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 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.11

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: rs545888691; hg19: chr22-24698029;