17-28364359-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001080837.4(SEBOX):​c.482C>G​(p.Ser161Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000501 in 1,596,780 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: SEBOX NM_001080837.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09865403).

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.482C>G	p.Ser161Cys	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.482C>G	p.Ser161Cys	missense	Exon 3 of 3	ENSP00000444503.3	Q9HB31
	ENSG00000273171	ENST00000555059.2	TSL:4	c.*333C>G		3_prime_UTR	Exon 4 of 4	ENSP00000452347.3	H0YJW9
	SARM1	ENST00000379061.8	TSL:2	n.4G>C		non_coding_transcript_exon	Exon 1 of 11

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000826 AC: 18 AN: 217934 AF XY: 0.0000594

Gnomad AFR exome AF: 0.0000788

Gnomad AMR exome AF: 0.0000661

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000103

Gnomad OTH exome AF: 0.000545

GnomAD4 exome AF: 0.0000526 AC: 76 AN: 1444598 Hom.: 0 Cov.: 34 AF XY: 0.0000544 AC XY: 39 AN XY: 717058

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

American (AMR) AF: 0.000121 AC: 5 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: 0.000203 AC: 17 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: 0.0000435 AC: 48 AN: 1103648

Other (OTH) AF: 0.000100 AC: 6 AN: 59856

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152182 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74340

African (AFR) AF: 0.0000241 AC: 1 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000135 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000497 AC: 6

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.90
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.099	T
MetaSVM	Uncertain	-0.13	T
PhyloP100		0.69
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.24
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.077	T
Vest4		0.18
MVP		0.11
ClinPred		0.036	T
GERP RS		2.6
gMVP		0.30
Mutation Taster		=100/0	polymorphism

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: rs782522084; hg19: chr17-26691381;