NM_001080837.4:c.542T>G

Variant names:

• chr17-28364299-A-C
• rs9910163
• NM_001080837.4:c.542T>G

Variant summary

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

The NM_001080837.4(SEBOX):​c.542T>G​(p.Leu181Trp) 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. 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SEBOX NM_001080837.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 26 publications found

Genes affected

SEBOX (HGNC:32942): (SEBOX homeobox) Homeodomain proteins, such as SEBOX, play a key role in coordinating gene expression during development (Cinquanta et al., 2000 [PubMed 10922053]).[supplied by OMIM, Mar 2008]

ENSG00000273171 (HGNC:):

SARM1 (HGNC:17074): (sterile alpha and TIR motif containing 1) Enables NAD+ nucleotidase, cyclic ADP-ribose generating and identical protein binding activity. Involved in NAD catabolic process; positive regulation of neuron death; and response to axon injury. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

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=0.12380049).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080837.4. 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
	SEBOX	NM_001080837.4	MANE Select	c.542T>G	p.Leu181Trp	missense	Exon 3 of 3	NP_001074306.3	Q9HB31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEBOX	ENST00000536498.6	TSL:5 MANE Select	c.542T>G	p.Leu181Trp	missense	Exon 3 of 3	ENSP00000444503.3	Q9HB31
	ENSG00000273171	ENST00000555059.2	TSL:4	c.*393T>G		3_prime_UTR	Exon 4 of 4	ENSP00000452347.3	H0YJW9
	ENSG00000258924	ENST00000591482.1	TSL:2	n.555+3452A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000425 AC: 1 AN: 235462 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000941

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000138 AC: 2 AN: 1453134 Hom.: 0 Cov.: 47 AF XY: 0.00000139 AC XY: 1 AN XY: 721874

African (AFR) AF: 0.00 AC: 0 AN: 33368

American (AMR) AF: 0.00 AC: 0 AN: 43286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39356

South Asian (SAS) AF: 0.00 AC: 0 AN: 84594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107852

Other (OTH) AF: 0.00 AC: 0 AN: 60100

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 144430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
PhyloP100		0.094
gMVP		0.54

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs9910163; hg19: chr17-26691321;