NM_080430.4:c.358C>T

Variant names:

• chr22-31105050-G-A
• rs548238752
• NM_080430.4:c.358C>T

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.358C>T​(p.Pro120Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P120T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SELENOM NM_080430.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.80
• 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]

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=0.21199584).

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.358C>T	p.Pro120Ser	missense	Exon 5 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.358C>T	p.Pro120Ser	missense	Exon 5 of 5	ENSP00000383155.2	Q8WWX9
	SELENOM	ENST00000402395.5	TSL:1	c.358C>T	p.Pro120Ser	missense	Exon 7 of 7	ENSP00000384564.1	Q8WWX9
	SELENOM	ENST00000490967.5	TSL:1	n.1797C>T		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459632 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726268

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33392

American (AMR) AF: 0.00 AC: 0 AN: 44240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111570

Other (OTH) AF: 0.00 AC: 0 AN: 60314

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.070
Eigen_PC	Benign	0.063
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.97	L
PhyloP100		4.8
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.15
Sift	Benign	0.14	T
Sift4G	Uncertain	0.023	D
Polyphen		0.29	B
Vest4		0.13
MutPred		0.26		Loss of loop (P = 0.0603)
MVP		0.40
MPC		0.86
ClinPred		0.84	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
Mutation Taster		=95/5	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: rs548238752; hg19: chr22-31501036;