chr22-31105023-C-T

Variant names:

• chr22-31105023-C-T
• rs371024549
• NM_080430.4:c.385G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080430.4(SELENOM):​c.385G>A​(p.Val129Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SELENOM NM_080430.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052759826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOM	NM_080430.4	c.385G>A	p.Val129Met	missense_variant	Exon 5 of 5	ENST00000400299.6	NP_536355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOM	ENST00000400299.6	c.385G>A	p.Val129Met	missense_variant	Exon 5 of 5	1	NM_080430.4	ENSP00000383155.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000417 AC: 1 AN: 239630 Hom.: 0 AF XY: 0.00000759 AC XY: 1 AN XY: 131682

Gnomad AFR exome AF: 0.0000690

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457022 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725004

Gnomad4 AFR exome AF: 0.0000302

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.0067	T;T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.73	.;T;T
MetaRNN	Benign	0.053	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;N;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.77	N;N;.
REVEL	Benign	0.047
Sift	Benign	0.082	T;T;.
Sift4G	Benign	0.12	T;T;T
Polyphen		0.45	P;P;.
Vest4		0.038
MutPred		0.17		Gain of disorder (P = 0.0508);Gain of disorder (P = 0.0508);.;
MVP		0.14
MPC		0.42
ClinPred		0.15	T
GERP RS		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.069

Splicing

Name	Calibrated prediction	Score	Prediction
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

LitVar

Other links and lift over

dbSNP: rs371024549; hg19: chr22-31501009; COSMIC: COSV60778839; COSMIC: COSV60778839;