rs782522084

Variant names:

• chr17-28364359-G-A
• rs782522084
• NM_001080837.4:c.482C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-28364359-G-A
• chr17-28364359-G-C

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.482C>T​(p.Ser161Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,444,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 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. S161C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: SEBOX NM_001080837.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.688
• 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: 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=0.09228811).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEBOX	NM_001080837.4	c.482C>T	p.Ser161Phe	missense_variant	Exon 3 of 3	ENST00000536498.6	NP_001074306.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEBOX	ENST00000536498.6	c.482C>T	p.Ser161Phe	missense_variant	Exon 3 of 3	5	NM_001080837.4	ENSP00000444503.3
ENSG00000273171	ENST00000555059.2	c.*333C>T		3_prime_UTR_variant	Exon 4 of 4	4		ENSP00000452347.3
SARM1	ENST00000379061.8	n.4G>A		non_coding_transcript_exon_variant	Exon 1 of 11	2
ENSG00000258924	ENST00000591482.1	n.555+3512G>A		intron_variant	Intron 5 of 5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1444598 Hom.: 0 Cov.: 34 AF XY: 0.00000279 AC XY: 2 AN XY: 717058

African (AFR) AF: 0.00 AC: 0 AN: 33158

American (AMR) AF: 0.00 AC: 0 AN: 41276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25776

East Asian (EAS) AF: 0.00 AC: 0 AN: 38908

South Asian (SAS) AF: 0.00 AC: 0 AN: 83902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52320

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

European-Non Finnish (NFE) AF: 0.00000362 AC: 4 AN: 1103648

Other (OTH) AF: 0.00 AC: 0 AN: 59856

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	11
DANN	Benign	0.72
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.56	T
PhyloP100		0.69
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.15
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.097	T
Vest4		0.14
MVP		0.12
ClinPred		0.16	T
GERP RS		2.6
gMVP		0.33
Mutation Taster		=100/0	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: rs782522084; hg19: chr17-26691381;