18-12984145-C-G

Position:

• chr18-12984145-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001013437.2(SEH1L):​c.1025C>G​(p.Thr342Ser) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T342N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SEH1L NM_001013437.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

Genes affected

SEH1L (HGNC:30379): (SEH1 like nucleoporin) The protein encoded by this gene is part of a nuclear pore complex, Nup107-160. This protein contains WD repeats and shares 34% amino acid identity with yeast Seh1 and 30% identity with yeast Sec13. All constituents of the Nup107-160 complex, including this protein, specifically localize to kinetochores in mitosis. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041244358).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEH1L	NM_001013437.2	c.1025C>G	p.Thr342Ser	missense_variant	8/9	ENST00000399892.7	NP_001013455.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEH1L	ENST00000399892.7	c.1025C>G	p.Thr342Ser	missense_variant	8/9	1	NM_001013437.2	ENSP00000382779	P3
SEH1L	ENST00000262124.15	c.1025C>G	p.Thr342Ser	missense_variant	8/9	1		ENSP00000262124	A1
SEH1L	ENST00000590843.1	n.2869C>G		non_coding_transcript_exon_variant	3/4	1
SEH1L	ENST00000592582.5	n.3548C>G		non_coding_transcript_exon_variant	5/6	1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	10
DANN	Benign	0.75
DEOGEN2	Benign	0.034	T;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.71
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.10	T;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.1	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.26	N;N
REVEL	Benign	0.054
Sift	Benign	0.58	T;T
Sift4G	Benign	0.84	T;T
Polyphen		0.0	B;B
Vest4		0.066
MutPred		0.26		Loss of sheet (P = 7e-04);Loss of sheet (P = 7e-04);
MVP		0.18
MPC		0.27
ClinPred		0.048	T
GERP RS		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.023
gMVP		0.091

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: rs6505776; hg19: chr18-12984144;