rs17419023

Variant names:

• chr10-97738603-C-T
• rs17419023
• NM_001385875.1:c.126C>T

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.126C>T​(p.Leu42Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00712 in 1,613,914 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0073 (49 hom.)
• Consequence: ZFYVE27 NM_001385875.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.392
• Publications: 5 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=-0.49).
• BP6: Variant 10-97738603-C-T is Benign according to our data. Variant chr10-97738603-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 238205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.392 with no splicing effect.
• BS2: High AC in GnomAd4 at 768 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.126C>T	p.Leu42Leu	synonymous	Exon 2 of 13	NP_001372804.1	Q5T4F4-1
	ZFYVE27	NM_001385876.1		c.126C>T	p.Leu42Leu	synonymous	Exon 2 of 13	NP_001372805.1
	ZFYVE27	NM_001002261.4		c.126C>T	p.Leu42Leu	synonymous	Exon 2 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.126C>T	p.Leu42Leu	synonymous	Exon 2 of 13	ENSP00000506975.1	Q5T4F4-1
	ZFYVE27	ENST00000393677.8	TSL:1	c.126C>T	p.Leu42Leu	synonymous	Exon 2 of 13	ENSP00000377282.3	Q5T4F4-1
	ZFYVE27	ENST00000423811.3	TSL:5	c.126C>T	p.Leu42Leu	synonymous	Exon 2 of 13	ENSP00000409594.2	Q5T4F4-3

Frequencies

GnomAD3 genomes AF: 0.00507 AC: 770 AN: 151912 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00688

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.0132

Gnomad NFE AF: 0.00840

Gnomad OTH AF: 0.00482

GnomAD2 exomes AF: 0.00489 AC: 1229 AN: 251496 AF XY: 0.00532

Gnomad AFR exome AF: 0.00160

Gnomad AMR exome AF: 0.00515

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00176

Gnomad NFE exome AF: 0.00708

Gnomad OTH exome AF: 0.00831

GnomAD4 exome AF: 0.00734 AC: 10723 AN: 1461880 Hom.: 49 Cov.: 33 AF XY: 0.00724 AC XY: 5264 AN XY: 727242

African (AFR) AF: 0.00105 AC: 35 AN: 33480

American (AMR) AF: 0.00521 AC: 233 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000727 AC: 19 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00435 AC: 375 AN: 86258

European-Finnish (FIN) AF: 0.00176 AC: 94 AN: 53418

Middle Eastern (MID) AF: 0.00832 AC: 48 AN: 5768

European-Non Finnish (NFE) AF: 0.00853 AC: 9480 AN: 1112006

Other (OTH) AF: 0.00727 AC: 439 AN: 60396

GnomAD4 genome AF: 0.00505 AC: 768 AN: 152034 Hom.: 4 Cov.: 32 AF XY: 0.00461 AC XY: 343 AN XY: 74350

African (AFR) AF: 0.00116 AC: 48 AN: 41442

American (AMR) AF: 0.00687 AC: 105 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00248 AC: 12 AN: 4834

European-Finnish (FIN) AF: 0.00123 AC: 13 AN: 10612

Middle Eastern (MID) AF: 0.0141 AC: 4 AN: 284

European-Non Finnish (NFE) AF: 0.00839 AC: 570 AN: 67944

Other (OTH) AF: 0.00429 AC: 9 AN: 2098

Alfa AF: 0.00652 Hom.: 7

Bravo AF: 0.00501

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00921

EpiControl AF: 0.00889

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.7
DANN	Benign	0.88
PhyloP100		0.39
Mutation Taster		=100/0	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: rs17419023; hg19: chr10-99498360; COSMIC: COSV100519453;