11-57741810-A-C

Position:

• chr11-57741810-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_170746.4(SELENOH):​c.124A>C​(p.Thr42Pro) variant causes a missense, splice region 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. 14/19 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SELENOH NM_170746.4 missense, splice_region
• Scores: Splicing: ADA: 0.1659
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45

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]

TMX2-CTNND1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17241189).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELENOH	NM_170746.4	c.124A>C	p.Thr42Pro	missense_variant, splice_region_variant	2/4	ENST00000534355.6
TMX2-CTNND1	NR_037646.1	n.346+4142A>C		intron_variant, non_coding_transcript_variant
SELENOH	NM_001321335.2	c.124A>C	p.Thr42Pro	missense_variant, splice_region_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELENOH	ENST00000534355.6	c.124A>C	p.Thr42Pro	missense_variant, splice_region_variant	2/4	1	NM_170746.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.124A>C (p.T42P) alteration is located in exon 2 (coding exon 2) of the C11orf31 gene. This alteration results from a A to C substitution at nucleotide position 124, causing the threonine (T) at amino acid position 42 to be replaced by a proline (P). 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	-0.012	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.020	T;T;T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.28	T;.;T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;L;L
MutationTaster	Benign	0.98	N;N
PROVEAN	Benign	-1.1	.;N;N
REVEL	Benign	0.12
Sift	Benign	0.26	.;T;T
Sift4G	Benign	0.27	T;T;T
Polyphen		0.77	.;P;P
Vest4		0.47
MutPred		0.45		Loss of MoRF binding (P = 0.0679);Loss of MoRF binding (P = 0.0679);Loss of MoRF binding (P = 0.0679);
MVP		0.64
MPC		0.18
ClinPred		0.59	D
GERP RS		4.1
Varity_R		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.17
dbscSNV1_RF	Benign	0.30
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-57509282;