22-31107498-A-G

Variant names:

• chr22-31107498-A-G
• NM_080430.4:c.8T>C

Variant summary

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

The NM_080430.4(SELENOM):​c.8T>C​(p.Leu3Pro) 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. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SELENOM NM_080430.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.177
• Publications: 0 publications found

Genes affected

SELENOM (HGNC:30397): (selenoprotein M) The protein encoded by this gene belongs to the selenoprotein M/SEP15 family. The exact function of this protein is not known. It is localized in the perinuclear region, is highly expressed in the brain, and may be involved in neurodegenerative disorders. Transgenic mice with targeted deletion of this gene exhibit increased weight gain, suggesting a role for this gene in the regulation of body weight and energy metabolism. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec). 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. [provided by RefSeq, Dec 2016]

LOC105372995 (HGNC:):

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=0.110701025).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080430.4. 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
	SELENOM	NM_080430.4	MANE Select	c.8T>C	p.Leu3Pro	missense	Exon 1 of 5	NP_536355.1	Q8WWX9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOM	ENST00000400299.6	TSL:1 MANE Select	c.8T>C	p.Leu3Pro	missense	Exon 1 of 5	ENSP00000383155.2	Q8WWX9
	SELENOM	ENST00000402395.5	TSL:1	c.8T>C	p.Leu3Pro	missense	Exon 3 of 7	ENSP00000384564.1	Q8WWX9
	SELENOM	ENST00000490967.5	TSL:1	n.36T>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1398296 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690704

African (AFR) AF: 0.00 AC: 0 AN: 31434

American (AMR) AF: 0.00 AC: 0 AN: 35954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24964

East Asian (EAS) AF: 0.00 AC: 0 AN: 35946

South Asian (SAS) AF: 0.00 AC: 0 AN: 79804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45776

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4260

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1082188

Other (OTH) AF: 0.00 AC: 0 AN: 57970

GnomAD4 genome Cov.: 32

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	0.064
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Benign	0.61
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.18
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.032
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.0010	B
Vest4		0.48
MutPred		0.28		Gain of relative solvent accessibility (P = 0.005)
MVP		0.20
MPC		0.67
ClinPred		0.054	T
GERP RS		2.3
PromoterAI		-0.17	Neutral
Varity_R		0.26
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

hg19: chr22-31503484;