rs9909629

Variant names:

• chr17-28385785-A-T
• rs9909629
• NM_015077.4:c.1630+510A>T

Variant summary

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

The NM_015077.4(SARM1):​c.1630+510A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,136 control chromosomes in the GnomAD database, including 1,068 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 0.11 (1068 hom., cov: 32)
• Consequence: SARM1 NM_015077.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.963
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SARM1	NM_015077.4	c.1630+510A>T		intron_variant	Intron 5 of 8	ENST00000585482.6	NP_055892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SARM1	ENST00000585482.6	c.1630+510A>T		intron_variant	Intron 5 of 8	1	NM_015077.4	ENSP00000468032.2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16640 AN: 152018 Hom.: 1055 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0809

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.110 AC: 16684 AN: 152136 Hom.: 1068 Cov.: 32 AF XY: 0.112 AC XY: 8366 AN XY: 74368

African (AFR) AF: 0.137 AC: 5680 AN: 41494

American (AMR) AF: 0.100 AC: 1531 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0809 AC: 281 AN: 3472

East Asian (EAS) AF: 0.231 AC: 1195 AN: 5168

South Asian (SAS) AF: 0.180 AC: 870 AN: 4822

European-Finnish (FIN) AF: 0.121 AC: 1285 AN: 10580

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0811 AC: 5515 AN: 67998

Other (OTH) AF: 0.113 AC: 238 AN: 2110

Alfa AF: 0.0935 Hom.: 101

Bravo AF: 0.108

Asia WGS AF: 0.230 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		0.96
Mutation Taster		=100/0	polymorphism (auto)

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: rs9909629; hg19: chr17-26712804;