Genetic Variant SPECC1L:p.Thr20Arg (chr22-24302290-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015330.6(SPECC1L):c.59C>G(p.Thr20Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T20M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

SPECC1L
NM_015330.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.35

Publications

0 publications found

Variant links:

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 links:

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]

SPECC1L-ADORA2A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08595994).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPECC1L	NM_015330.6	MANE Select	c.59C>G	p.Thr20Arg	missense	Exon 3 of 17	NP_056145.5	Q69YQ0-1
SPECC1L	NM_001145468.4		c.59C>G	p.Thr20Arg	missense	Exon 2 of 16	NP_001138940.4	Q69YQ0-1
SPECC1L	NM_001254732.3		c.59C>G	p.Thr20Arg	missense	Exon 2 of 15	NP_001241661.3	Q69YQ0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPECC1L	ENST00000314328.14	TSL:1 MANE Select	c.59C>G	p.Thr20Arg	missense	Exon 3 of 17	ENSP00000325785.8	Q69YQ0-1
SPECC1L	ENST00000437398.5	TSL:1	c.59C>G	p.Thr20Arg	missense	Exon 2 of 16	ENSP00000393363.1	Q69YQ0-1
SPECC1L-ADORA2A	ENST00000358654.2	TSL:2	n.59C>G		non_coding_transcript_exon	Exon 3 of 20	ENSP00000351480.2	F8WAN1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.96

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.83

M_CAP

Benign

0.013

MetaRNN

Benign

0.086

MetaSVM

Benign

-1.0

PhyloP100

2.3

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.21

REVEL

Benign

0.052

Sift

Benign

0.38

Sift4G

Benign

0.35

Vest4

0.41

MutPred

0.28

Gain of solvent accessibility (P = 0.0055)

MVP

0.52

MPC

0.48

ClinPred

0.15

GERP RS

2.7

gMVP

0.23

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over