rs144766472

Variant names:

• chr22-26292655-C-A
• NM_021115.5:c.344C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-26292655-C-A
• chr22-26292655-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021115.5(SEZ6L):​c.344C>A​(p.Pro115His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SEZ6L NM_021115.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09809074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEZ6L	NM_021115.5	c.344C>A	p.Pro115His	missense_variant	Exon 2 of 17	ENST00000248933.11	NP_066938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEZ6L	ENST00000248933.11	c.344C>A	p.Pro115His	missense_variant	Exon 2 of 17	1	NM_021115.5	ENSP00000248933.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461018 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726820

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0089	.;T;.;.;T;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.77	T;T;T;T;T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.098	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;.;N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.17	N;N;N;.;N;N
REVEL	Benign	0.029
Sift	Uncertain	0.026	D;D;D;.;D;D
Sift4G	Uncertain	0.036	D;D;D;D;D;D
Polyphen		0.41, 0.94, 0.21, 0.55	.;B;P;.;B;P
Vest4		0.22
MutPred		0.21		Loss of glycosylation at P115 (P = 0.0024);Loss of glycosylation at P115 (P = 0.0024);Loss of glycosylation at P115 (P = 0.0024);Loss of glycosylation at P115 (P = 0.0024);Loss of glycosylation at P115 (P = 0.0024);Loss of glycosylation at P115 (P = 0.0024);
MVP		0.093
MPC		0.30
ClinPred		0.20	T
GERP RS		2.6
Varity_R		0.060
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-26688621;