14-67754215-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015346.4(ZFYVE26):​c.6987-3C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZFYVE26
NM_015346.4 splice_region, intron

Scores

2
Splicing: ADA: 0.4025
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.389
Variant links:
Genes affected
ZFYVE26 (HGNC:20761): (zinc finger FYVE-type containing 26) This gene encodes a protein which contains a FYVE zinc finger binding domain. The presence of this domain is thought to target these proteins to membrane lipids through interaction with phospholipids in the membrane. Mutations in this gene are associated with autosomal recessive spastic paraplegia-15. [provided by RefSeq, Oct 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZFYVE26NM_015346.4 linkc.6987-3C>A splice_region_variant, intron_variant Intron 37 of 41 ENST00000347230.9 NP_056161.2 Q68DK2-1
ZFYVE26XM_047431173.1 linkc.6987-3C>A splice_region_variant, intron_variant Intron 37 of 41 XP_047287129.1
ZFYVE26XM_047431174.1 linkc.4662-3C>A splice_region_variant, intron_variant Intron 26 of 30 XP_047287130.1
ZFYVE26XM_047431175.1 linkc.4569-3C>A splice_region_variant, intron_variant Intron 26 of 30 XP_047287131.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZFYVE26ENST00000347230.9 linkc.6987-3C>A splice_region_variant, intron_variant Intron 37 of 41 1 NM_015346.4 ENSP00000251119.5 Q68DK2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251378
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135872
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461832
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.75
DANN
Benign
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.40
dbscSNV1_RF
Benign
0.37
SpliceAI score (max)
0.87
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.87
Position offset: -3

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs76728509; hg19: chr14-68220932; API