Variant chr11-57741608-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_170746.4(SELENOH):c.13G>T(p.Gly5Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000267 in 1,121,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SELENOH
NM_170746.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.98

Variant links:

Genes affected

SELENOH (HGNC:18251): (selenoprotein H) This gene encodes a nucleolar protein, which belongs to the SelWTH family. It functions as an oxidoreductase, and has been shown to protect neurons against UVB-induced damage by inhibiting apoptotic cell death pathways, promote mitochondrial biogenesis and mitochondrial function, and suppress cellular senescence through genome maintenance and redox regulation. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2016]

SELENOH links:

TMX2-CTNND1 (HGNC:):

TMX2-CTNND1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2903133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SELENOH	NM_170746.4 linkuse as main transcript	c.13G>T	p.Gly5Trp	missense_variant	1/4	ENST00000534355.6
TMX2-CTNND1	NR_037646.1 linkuse as main transcript	n.346+3940G>T		intron_variant, non_coding_transcript_variant
SELENOH	NM_001321335.2 linkuse as main transcript	c.13G>T	p.Gly5Trp	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SELENOH	ENST00000534355.6 linkuse as main transcript	c.13G>T	p.Gly5Trp	missense_variant	1/4	1	NM_170746.4	P1
SELENOH	ENST00000388857.8 linkuse as main transcript	c.13G>T	p.Gly5Trp	missense_variant	1/3	1		P1
SELENOH	ENST00000533321.1 linkuse as main transcript	n.96G>T		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000267

AC:

AN:

1121766

Hom.:

Cov.:

AF XY:

0.00000188

AC XY:

AN XY:

532940

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000907

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000841

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.13G>T (p.G5W) alteration is located in exon 1 (coding exon 1) of the C11orf31 gene. This alteration results from a G to T substitution at nucleotide position 13, causing the glycine (G) at amino acid position 5 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.039

T;T;T

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.60

T;.;T

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.69

.;N;N

MutationTaster

Benign

0.91

D;D

PROVEAN

Uncertain

-3.0

.;D;D

REVEL

Benign

0.087

Sift

Uncertain

0.0020

.;D;D

Sift4G

Uncertain

0.017

D;D;D

Polyphen

0.99

.;D;D

Vest4

0.45

MutPred

0.33

Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);

MVP

0.35

MPC

0.26

ClinPred

0.95

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over