18-12984145-C-G

Variant names:

• chr18-12984145-C-G
• rs6505776
• NM_001013437.2:c.1025C>G
• SEH1L p.Thr342Ser

Variant summary

Our verdict is Likely benign. The variant received -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. 17/22 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: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013437.2. 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
	SEH1L	NM_001013437.2	MANE Select	c.1025C>G	p.Thr342Ser	missense	Exon 8 of 9	NP_001013455.1	Q96EE3-1
	SEH1L	NM_031216.4		c.1025C>G	p.Thr342Ser	missense	Exon 8 of 9	NP_112493.2	Q96EE3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEH1L	ENST00000399892.7	TSL:1 MANE Select	c.1025C>G	p.Thr342Ser	missense	Exon 8 of 9	ENSP00000382779.1	Q96EE3-1
	SEH1L	ENST00000262124.15	TSL:1	c.1025C>G	p.Thr342Ser	missense	Exon 8 of 9	ENSP00000262124.10	Q96EE3-2
	SEH1L	ENST00000590843.1	TSL:1	n.2869C>G		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.1	N
PhyloP100		1.4
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.054
Sift	Benign	0.58	T
Sift4G	Benign	0.84	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.023
gMVP		0.091
Mutation Taster		=94/6	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6505776; hg19: chr18-12984144;