18-12986891-G-C

Variant names:

• chr18-12986891-G-C
• rs372017827
• NM_001013437.2:c.1100G>C

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.1100G>C​(p.Arg367Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000579 in 1,606,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: SEH1L NM_001013437.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77
• Publications: 1 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]

CEP192-DT (HGNC:55313): (CEP192 divergent transcript)

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=0.17722031).

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.1100G>C	p.Arg367Pro	missense	Exon 9 of 9	NP_001013455.1	Q96EE3-1
	SEH1L	NM_031216.4		c.*1639G>C		3_prime_UTR	Exon 9 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.1100G>C	p.Arg367Pro	missense	Exon 9 of 9	ENSP00000382779.1	Q96EE3-1
	SEH1L	ENST00000262124.15	TSL:1	c.*1639G>C		3_prime_UTR	Exon 9 of 9	ENSP00000262124.10	Q96EE3-2
	SEH1L	ENST00000590843.1	TSL:1	n.4566G>C		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.0000861 AC: 13 AN: 151028 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000583

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000815 AC: 20 AN: 245382 AF XY: 0.0000979

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000605

Gnomad NFE exome AF: 0.0000635

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000550 AC: 80 AN: 1455106 Hom.: 0 Cov.: 32 AF XY: 0.0000635 AC XY: 46 AN XY: 724088

African (AFR) AF: 0.00 AC: 0 AN: 33140

American (AMR) AF: 0.00 AC: 0 AN: 44342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25902

East Asian (EAS) AF: 0.00 AC: 0 AN: 39358

South Asian (SAS) AF: 0.00 AC: 0 AN: 85740

European-Finnish (FIN) AF: 0.000658 AC: 35 AN: 53156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.0000370 AC: 41 AN: 1107726

Other (OTH) AF: 0.0000667 AC: 4 AN: 60010

GnomAD4 genome AF: 0.0000861 AC: 13 AN: 151028 Hom.: 0 Cov.: 32 AF XY: 0.0000815 AC XY: 6 AN XY: 73620

African (AFR) AF: 0.00 AC: 0 AN: 41016

American (AMR) AF: 0.00 AC: 0 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.00 AC: 0 AN: 4790

European-Finnish (FIN) AF: 0.000583 AC: 6 AN: 10288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67856

Other (OTH) AF: 0.00 AC: 0 AN: 2070

Alfa AF: 0.000108 Hom.: 0

Bravo AF: 0.0000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000494 AC: 6

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	0.19
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Benign	0.93
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.97	T
PhyloP100		3.8
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.10
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.15	T
Polyphen		0.086	B
Vest4		0.57
MVP		0.47
MPC		0.97
ClinPred		0.19	T
GERP RS		0.063
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
gMVP		0.79
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs372017827; hg19: chr18-12986890;