rs12941604

Positions:

• chr17-48929651-G-A
• chr17-48929651-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007241.4(SNF8):​c.*824C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,156 control chromosomes in the GnomAD database, including 1,442 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 0.13 (1442 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SNF8 NM_007241.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

Genes affected

SNF8 (HGNC:17028): (SNF8 subunit of ESCRT-II) The protein encoded by this gene is a component of the endosomal sorting complex required for transport II (ESCRT-II), which regulates the movement of ubiquitinylated transmembrane proteins to the lysosome for degradation. This complex also interacts with the RNA polymerase II elongation factor (ELL) to overcome the repressive effects of ELL on RNA polymerase II activity. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

SNF8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNF8	NM_007241.4	c.*824C>T		3_prime_UTR_variant	8/8	ENST00000502492.6	NP_009172.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNF8	ENST00000502492	c.*824C>T		3_prime_UTR_variant	8/8	1	NM_007241.4	ENSP00000421380.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20202 AN: 152038 Hom.: 1438 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0938

Gnomad ASJ AF: 0.0986

Gnomad EAS AF: 0.0811

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.160

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.133 AC: 20219 AN: 152156 Hom.: 1442 Cov.: 32 AF XY: 0.128 AC XY: 9535 AN XY: 74386

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0936

Gnomad4 ASJ AF: 0.0986

Gnomad4 EAS AF: 0.0813

Gnomad4 SAS AF: 0.0647

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.158

Alfa AF: 0.134 Hom.: 2007

Bravo AF: 0.130

Asia WGS AF: 0.0800 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.097
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs12941604; hg19: chr17-47007013;