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

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001385875.1(ZFYVE27):​c.664+114T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 846,468 control chromosomes in the GnomAD database, including 205,878 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (34736 hom., cov: 32)
  • Exomes 𝑓: 0.70 (171142 hom.)
• Consequence: ZFYVE27 NM_001385875.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-97749700-T-G is Benign according to our data. Variant chr10-97749700-T-G is described in ClinVar as Benign. ClinVar VariationId is 1237014.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

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>G		intron	N/A	NP_001372804.1
	ZFYVE27	NM_001385876.1		c.703+114T>G		intron	N/A	NP_001372805.1
	ZFYVE27	NM_001002261.4		c.664+114T>G		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>G		intron	N/A	ENSP00000506975.1
	ZFYVE27	ENST00000393677.8	TSL:1	c.664+114T>G		intron	N/A	ENSP00000377282.3
	ZFYVE27	ENST00000423811.3	TSL:5	c.664+114T>G		intron	N/A	ENSP00000409594.2

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102094 AN: 151920 Hom.: 34726 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.663

GnomAD4 exome AF: 0.697 AC: 484301 AN: 694430 Hom.: 171142 AF XY: 0.696 AC XY: 258677 AN XY: 371430

African (AFR) AF: 0.591 AC: 10949 AN: 18514

American (AMR) AF: 0.549 AC: 21236 AN: 38700

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 15647 AN: 20964

East Asian (EAS) AF: 0.510 AC: 17846 AN: 34996

South Asian (SAS) AF: 0.637 AC: 43815 AN: 68736

European-Finnish (FIN) AF: 0.777 AC: 36732 AN: 47276

Middle Eastern (MID) AF: 0.714 AC: 2303 AN: 3224

European-Non Finnish (NFE) AF: 0.730 AC: 311731 AN: 427140

Other (OTH) AF: 0.689 AC: 24042 AN: 34880

GnomAD4 genome AF: 0.672 AC: 102135 AN: 152038 Hom.: 34736 Cov.: 32 AF XY: 0.672 AC XY: 49937 AN XY: 74316

African (AFR) AF: 0.592 AC: 24558 AN: 41464

American (AMR) AF: 0.606 AC: 9261 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 2573 AN: 3470

East Asian (EAS) AF: 0.479 AC: 2476 AN: 5164

South Asian (SAS) AF: 0.658 AC: 3172 AN: 4818

European-Finnish (FIN) AF: 0.787 AC: 8315 AN: 10570

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.728 AC: 49498 AN: 67966

Other (OTH) AF: 0.666 AC: 1406 AN: 2112

Alfa AF: 0.699 Hom.: 47466

Bravo AF: 0.651

Asia WGS AF: 0.601 AC: 2091 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	16
DANN	Benign	0.80
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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; COSMIC: COSV61746638; COSMIC: COSV61746638;