10-97749700-T-G

Position:

• chr10-97749700-T-G

Variant summary

Our verdict is Benign. Variant got -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, single submitter B:1
• Conservation: PhyloP100: 1.31

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFYVE27	NM_001385875.1	c.664+114T>G		intron_variant		ENST00000684270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFYVE27	ENST00000684270.1	c.664+114T>G		intron_variant			NM_001385875.1	A1

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

Gnomad4 AFR exome AF: 0.591

Gnomad4 AMR exome AF: 0.549

Gnomad4 ASJ exome AF: 0.746

Gnomad4 EAS exome AF: 0.510

Gnomad4 SAS exome AF: 0.637

Gnomad4 FIN exome AF: 0.777

Gnomad4 NFE exome AF: 0.730

Gnomad4 OTH exome AF: 0.689

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

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.741

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.666

Alfa AF: 0.707 Hom.: 37016

Bravo AF: 0.651

Asia WGS AF: 0.601 AC: 2091 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	16
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs946778; hg19: chr10-99509457; COSMIC: COSV61746638; COSMIC: COSV61746638;