rs1994970

Variant names:

• chr17-48936765-T-A
• rs1994970
• NM_007241.4:c.349+255A>T

Your query was ambiguous. Multiple possible variants found:

• chr17-48936765-T-A
• chr17-48936765-T-C
• chr17-48936765-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007241.4(SNF8):​c.349+255A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SNF8 NM_007241.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455
• Publications: 18 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):

• neurodevelopmental disorder plus optic atrophy

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

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000230532 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNF8	NM_007241.4	c.349+255A>T		intron_variant	Intron 4 of 7	ENST00000502492.6	NP_009172.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNF8	ENST00000502492.6	c.349+255A>T		intron_variant	Intron 4 of 7	1	NM_007241.4	ENSP00000421380.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 373308 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 196052

African (AFR) AF: 0.00 AC: 0 AN: 11130

American (AMR) AF: 0.00 AC: 0 AN: 14160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11768

East Asian (EAS) AF: 0.00 AC: 0 AN: 25996

South Asian (SAS) AF: 0.00 AC: 0 AN: 35814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1672

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 227460

Other (OTH) AF: 0.00 AC: 0 AN: 21902

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	10
DANN	Benign	0.82
PhyloP100		0.46

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: rs1994970; hg19: chr17-47014127;