22-26169685-C-A

Variant names:

• chr22-26169685-C-A
• NM_021115.5:c.16C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021115.5(SEZ6L):​c.16C>A​(p.Pro6Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SEZ6L NM_021115.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.632
• Publications: 0 publications found

Genes affected

SEZ6L (HGNC:10763): (seizure related 6 homolog like) Predicted to act upstream of or within adult locomotory behavior; nervous system development; and regulation of protein kinase C signaling. Predicted to be located in endoplasmic reticulum and neuronal cell body. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000229770 (HGNC:):

ACMG classification

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=0.2350052).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021115.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEZ6L	NM_021115.5	MANE Select	c.16C>A	p.Pro6Thr	missense	Exon 1 of 17	NP_066938.2
	SEZ6L	NM_001184773.2		c.16C>A	p.Pro6Thr	missense	Exon 1 of 17	NP_001171702.1	Q9BYH1-6
	SEZ6L	NM_001184774.2		c.16C>A	p.Pro6Thr	missense	Exon 1 of 16	NP_001171703.1	Q9BYH1-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEZ6L	ENST00000248933.11	TSL:1 MANE Select	c.16C>A	p.Pro6Thr	missense	Exon 1 of 17	ENSP00000248933.6	Q9BYH1-1
	SEZ6L	ENST00000404234.7	TSL:1	c.16C>A	p.Pro6Thr	missense	Exon 1 of 17	ENSP00000384772.3	Q9BYH1-6
	SEZ6L	ENST00000629590.2	TSL:1	c.16C>A	p.Pro6Thr	missense	Exon 1 of 16	ENSP00000485720.1	Q9BYH1-7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1163584 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 564586

African (AFR) AF: 0.00 AC: 0 AN: 23796

American (AMR) AF: 0.00 AC: 0 AN: 13108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16840

East Asian (EAS) AF: 0.00 AC: 0 AN: 27094

South Asian (SAS) AF: 0.00 AC: 0 AN: 42968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3196

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 963552

Other (OTH) AF: 0.00 AC: 0 AN: 46688

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0055	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.68	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.63
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	0.12	N
REVEL	Benign	0.10
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.26		Gain of phosphorylation at P6 (P = 0.0265)
MVP		0.043
MPC		0.11
ClinPred		0.86	D
GERP RS		3.7
PromoterAI		-0.068	Neutral
Varity_R		0.17
gMVP		0.37
Mutation Taster		=82/18	polymorphism

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

hg19: chr22-26565651;