rs143515214

Variant names:

• chr10-97748335-G-A
• rs143515214
• NM_001385875.1:c.522G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001385875.1(ZFYVE27):​c.522G>A​(p.Leu174Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000564 in 1,614,146 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00059 (1 hom.)
• Consequence: ZFYVE27 NM_001385875.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.137
• Publications: 0 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: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 10-97748335-G-A is Benign according to our data. Variant chr10-97748335-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 301835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.137 with no splicing effect.
• BS2: High AC in GnomAd4 at 50 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE27	NM_001385875.1	MANE Select	c.522G>A	p.Leu174Leu	synonymous	Exon 5 of 13	NP_001372804.1	Q5T4F4-1
	ZFYVE27	NM_001385876.1		c.561G>A	p.Leu187Leu	synonymous	Exon 6 of 13	NP_001372805.1
	ZFYVE27	NM_001002261.4		c.522G>A	p.Leu174Leu	synonymous	Exon 5 of 13	NP_001002261.1	Q5T4F4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE27	ENST00000684270.1	MANE Select	c.522G>A	p.Leu174Leu	synonymous	Exon 5 of 13	ENSP00000506975.1	Q5T4F4-1
	ZFYVE27	ENST00000393677.8	TSL:1	c.522G>A	p.Leu174Leu	synonymous	Exon 5 of 13	ENSP00000377282.3	Q5T4F4-1
	ZFYVE27	ENST00000423811.3	TSL:5	c.522G>A	p.Leu174Leu	synonymous	Exon 5 of 13	ENSP00000409594.2	Q5T4F4-3

Frequencies

GnomAD3 genomes AF: 0.000329 AC: 50 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000371 AC: 93 AN: 250962 AF XY: 0.000361

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000929

Gnomad NFE exome AF: 0.000749

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000588 AC: 860 AN: 1461826 Hom.: 1 Cov.: 31 AF XY: 0.000587 AC XY: 427 AN XY: 727220

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.000157 AC: 7 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.000506 AC: 27 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000720 AC: 801 AN: 1112000

Other (OTH) AF: 0.000381 AC: 23 AN: 60392

GnomAD4 genome AF: 0.000328 AC: 50 AN: 152320 Hom.: 0 Cov.: 33 AF XY: 0.000282 AC XY: 21 AN XY: 74466

African (AFR) AF: 0.0000962 AC: 4 AN: 41566

American (AMR) AF: 0.000196 AC: 3 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68042

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000495 Hom.: 1

Bravo AF: 0.000257

EpiCase AF: 0.000164

EpiControl AF: 0.000711

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hereditary spastic paraplegia 33 (2)
-	-	1	not provided (1)
-	-	1	Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.7
DANN	Benign	0.75
PhyloP100		-0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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: rs143515214; hg19: chr10-99508092;