NM_001080837.4:c.-11T>C

Variant names:

• chr17-28365162-A-G
• NM_001080837.4:c.-11T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001080837.4(SEBOX):​c.-11T>C variant causes a 5 prime UTR premature start codon gain 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEBOX NM_001080837.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.324
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.112).
• BP6: Variant 17-28365162-A-G is Benign according to our data. Variant chr17-28365162-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3159096.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-11T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001074306.3	Q9HB31
	SEBOX	NM_001080837.4	MANE Select	c.-11T>C		5_prime_UTR	Exon 1 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.-11T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000444503.3	Q9HB31
	SEBOX	ENST00000536498.6	TSL:5 MANE Select	c.-11T>C		5_prime_UTR	Exon 1 of 3	ENSP00000444503.3	Q9HB31
	ENSG00000273171	ENST00000555059.2	TSL:4	c.330-207T>C		intron	N/A	ENSP00000452347.3	H0YJW9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.86
DANN	Benign	0.61
PhyloP100		-0.32
PromoterAI		-0.0016	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr17-26692184;