17-28392606-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SARM1	NM_015077.4	c.1924-3299T>C		intron_variant		ENST00000585482.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SARM1	ENST00000585482.6	c.1924-3299T>C		intron_variant		1	NM_015077.4	P1

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

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.896

Gnomad4 ASJ AF: 0.920

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.879

Gnomad4 NFE AF: 0.919

Gnomad4 OTH AF: 0.886

Alfa AF: 0.894 Hom.: 10875

Bravo AF: 0.882

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.7

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9894260; hg19: chr17-26719625;