17-28392606-T-C

Variant names:

• chr17-28392606-T-C
• rs9894260
• NM_015077.4:c.1924-3299T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015077.4(SARM1):​c.1924-3299T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,204 control chromosomes in the GnomAD database, including 59,339 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (59339 hom., cov: 32)
• Consequence: SARM1 NM_015077.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475
• Publications: 16 publications found

Genes affected

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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015077.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARM1	NM_015077.4	MANE Select	c.1924-3299T>C		intron	N/A	NP_055892.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARM1	ENST00000585482.6	TSL:1 MANE Select	c.1924-3299T>C		intron	N/A	ENSP00000468032.2
	SARM1	ENST00000578128.5	TSL:3	c.520-3299T>C		intron	N/A	ENSP00000462479.1
	SARM1	ENST00000579593.1	TSL:5	c.196-3299T>C		intron	N/A	ENSP00000462228.1

Frequencies

GnomAD3 genomes AF: 0.882 AC: 134091 AN: 152086 Hom.: 59312 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.919

Gnomad OTH AF: 0.889

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.881 AC: 134166 AN: 152204 Hom.: 59339 Cov.: 32 AF XY: 0.879 AC XY: 65437 AN XY: 74416

African (AFR) AF: 0.832 AC: 34523 AN: 41502

American (AMR) AF: 0.896 AC: 13705 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3194 AN: 3472

East Asian (EAS) AF: 0.770 AC: 3980 AN: 5166

South Asian (SAS) AF: 0.820 AC: 3956 AN: 4826

European-Finnish (FIN) AF: 0.879 AC: 9315 AN: 10596

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.919 AC: 62499 AN: 68024

Other (OTH) AF: 0.886 AC: 1875 AN: 2116

Alfa AF: 0.890 Hom.: 21080

Bravo AF: 0.882

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
PhyloP100		-0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9894260; hg19: chr17-26719625;