rs12941604

Variant names:

• chr17-48929651-G-A
• rs12941604
• NM_007241.4:c.*824C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy 115

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• neurodevelopmental disorder plus optic atrophy

  Inheritance: AR Classification: MODERATE Submitted by: G2P, PanelApp Australia
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007241.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNF8	NM_007241.4	MANE Select	c.*824C>T		3_prime_UTR	Exon 8 of 8	NP_009172.2
	SNF8	NM_001317192.2		c.*824C>T		3_prime_UTR	Exon 8 of 8	NP_001304121.1	Q96H20-2
	SNF8	NM_001317193.2		c.*824C>T		3_prime_UTR	Exon 7 of 7	NP_001304122.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNF8	ENST00000502492.6	TSL:1 MANE Select	c.*824C>T		3_prime_UTR	Exon 8 of 8	ENSP00000421380.1	Q96H20-1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.145 AC: 6019 AN: 41498

American (AMR) AF: 0.0936 AC: 1431 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0986 AC: 342 AN: 3470

East Asian (EAS) AF: 0.0813 AC: 421 AN: 5178

South Asian (SAS) AF: 0.0647 AC: 312 AN: 4822

European-Finnish (FIN) AF: 0.140 AC: 1487 AN: 10592

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9755 AN: 68000

Other (OTH) AF: 0.158 AC: 334 AN: 2108

Alfa AF: 0.134 Hom.: 2806

Bravo AF: 0.130

Asia WGS AF: 0.0800 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.097
DANN	Benign	0.74
PhyloP100		-1.7
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: rs12941604; hg19: chr17-47007013;