NM_001385875.1:c.664+114T>C

Variant names:

• chr10-97749700-T-C
• rs946778
• NM_001385875.1:c.664+114T>C

Variant summary

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

The NM_001385875.1(ZFYVE27):​c.664+114T>C 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: 32)
• Consequence: ZFYVE27 NM_001385875.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 8 publications found

Genes affected

ZFYVE27 (HGNC:26559): (zinc finger FYVE-type containing 27) This gene encodes a protein with several transmembrane domains, a Rab11-binding domain and a lipid-binding FYVE finger domain. The encoded protein appears to promote neurite formation. A mutation in this gene has been reported to be associated with hereditary spastic paraplegia, however the pathogenicity of the mutation, which may simply represent a polymorphism, is unclear. [provided by RefSeq, Mar 2010]

ZFYVE27 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 33

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

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=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385875.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE27	NM_001385875.1	MANE Select	c.664+114T>C		intron	N/A	NP_001372804.1
	ZFYVE27	NM_001385876.1		c.703+114T>C		intron	N/A	NP_001372805.1
	ZFYVE27	NM_001002261.4		c.664+114T>C		intron	N/A	NP_001002261.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE27	ENST00000684270.1	MANE Select	c.664+114T>C		intron	N/A	ENSP00000506975.1
	ZFYVE27	ENST00000393677.8	TSL:1	c.664+114T>C		intron	N/A	ENSP00000377282.3
	ZFYVE27	ENST00000423811.3	TSL:5	c.664+114T>C		intron	N/A	ENSP00000409594.2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	17
DANN	Benign	0.86
PhyloP100		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs946778; hg19: chr10-99509457;