rs782660798

Variant names:

• chr17-28364428-C-A
• rs782660798
• NM_001080837.4:c.413G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-28364428-C-A
• chr17-28364428-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080837.4(SEBOX):​c.413G>T​(p.Arg138Leu) 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. 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. R138W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEBOX NM_001080837.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584
• 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 (MetaRNN=0.055920392).

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.413G>T	p.Arg138Leu	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.413G>T	p.Arg138Leu	missense	Exon 3 of 3	ENSP00000444503.3	Q9HB31
	ENSG00000273171	ENST00000555059.2	TSL:4	c.*264G>T		3_prime_UTR	Exon 4 of 4	ENSP00000452347.3	H0YJW9
	SARM1	ENST00000379061.8	TSL:2	n.73C>A		non_coding_transcript_exon	Exon 1 of 11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	8.4
DANN	Benign	0.59
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.67	T
PhyloP100		0.58
PrimateAI	Benign	0.32	T
REVEL	Benign	0.15
Sift4G	Benign	0.82	T
Vest4		0.095
MVP		0.048
ClinPred		0.10	T
GERP RS		4.0
gMVP		0.30

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

Other links and lift over

dbSNP: rs782660798; hg19: chr17-26691450;