rs782598601

Variant names:

• chr17-28364393-A-G
• rs782598601
• NM_001080837.4:c.448T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-28364393-A-G
• chr17-28364393-A-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001080837.4(SEBOX):​c.448T>C​(p.Trp150Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000245 in 1,591,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: SEBOX NM_001080837.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.168
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051652372).
• BP6: Variant 17-28364393-A-G is Benign according to our data. Variant chr17-28364393-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3159095.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEBOX	NM_001080837.4	c.448T>C	p.Trp150Arg	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.448T>C	p.Trp150Arg	missense_variant	Exon 3 of 3	5	NM_001080837.4	ENSP00000444503.3
ENSG00000273171	ENST00000555059.2	c.*299T>C		3_prime_UTR_variant	Exon 4 of 4	4		ENSP00000452347.3
SARM1	ENST00000379061.8	n.38A>G		non_coding_transcript_exon_variant	Exon 1 of 11	2
ENSG00000258924	ENST00000591482.1	n.555+3546A>G		intron_variant	Intron 5 of 5	2

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152142 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.0000288 AC: 6 AN: 208686 AF XY: 0.0000266

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: 0.0000547

Gnomad OTH exome AF: 0.000187

GnomAD4 exome AF: 0.0000208 AC: 30 AN: 1438924 Hom.: 0 Cov.: 34 AF XY: 0.0000210 AC XY: 15 AN XY: 713856

African (AFR) AF: 0.0000303 AC: 1 AN: 33034

American (AMR) AF: 0.00 AC: 0 AN: 39966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25696

East Asian (EAS) AF: 0.00 AC: 0 AN: 38618

South Asian (SAS) AF: 0.00 AC: 0 AN: 83778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52012

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5732

European-Non Finnish (NFE) AF: 0.0000200 AC: 22 AN: 1100460

Other (OTH) AF: 0.0000839 AC: 5 AN: 59628

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152142 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74320

African (AFR) AF: 0.0000483 AC: 2 AN: 41436

American (AMR) AF: 0.000262 AC: 4 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000415 AC: 5

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 14, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.9
DANN	Benign	0.44
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.70	T
PhyloP100		0.17
PrimateAI	Benign	0.28	T
REVEL	Benign	0.26
Sift4G	Benign	0.44	T
Vest4		0.11
MVP		0.048
ClinPred		0.017	T
GERP RS		-1.8
gMVP		0.21
Mutation Taster		=94/6	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: rs782598601; hg19: chr17-26691415;