18-12984145-C-T

Variant names:

• chr18-12984145-C-T
• rs6505776
• NM_001013437.2:c.1025C>T

Variant summary

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

The NM_001013437.2(SEH1L):​c.1025C>T​(p.Thr342Ile) 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. 16/22 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: 34)
• Consequence: SEH1L NM_001013437.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 53 publications found

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

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=0.06902984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEH1L	NM_001013437.2	c.1025C>T	p.Thr342Ile	missense_variant	Exon 8 of 9	ENST00000399892.7	NP_001013455.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEH1L	ENST00000399892.7	c.1025C>T	p.Thr342Ile	missense_variant	Exon 8 of 9	1	NM_001013437.2	ENSP00000382779.1
SEH1L	ENST00000262124.15	c.1025C>T	p.Thr342Ile	missense_variant	Exon 8 of 9	1		ENSP00000262124.10
SEH1L	ENST00000590843.1	n.2869C>T		non_coding_transcript_exon_variant	Exon 3 of 4	1
SEH1L	ENST00000592582.5	n.3548C>T		non_coding_transcript_exon_variant	Exon 5 of 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	0.079
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.077	T;.
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;N
PhyloP100		1.4
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.061
Sift	Benign	0.034	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.020	B;B
Vest4		0.12
MutPred		0.29		Loss of loop (P = 0.0022);Loss of loop (P = 0.0022);
MVP		0.18
MPC		0.32
ClinPred		0.43	T
GERP RS		1.0
Varity_R		0.045
gMVP		0.27
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

dbSNP: rs6505776; hg19: chr18-12984144;