rs7156492

Variant names:

• chr14-67785952-G-A
• rs7156492
• NM_015346.4:c.3210C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-67785952-G-A
• chr14-67785952-G-C
• chr14-67785952-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_015346.4(ZFYVE26):​c.3210C>T​(p.Pro1070Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,614,144 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P1070P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0014 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (25 hom.)
• Consequence: ZFYVE26 NM_015346.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0830
• Publications: 7 publications found

Genes affected

ZFYVE26 (HGNC:20761): (zinc finger FYVE-type containing 26) This gene encodes a protein which contains a FYVE zinc finger binding domain. The presence of this domain is thought to target these proteins to membrane lipids through interaction with phospholipids in the membrane. Mutations in this gene are associated with autosomal recessive spastic paraplegia-15. [provided by RefSeq, Oct 2008]

ZFYVE26 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 15

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Myriad Women’s Health

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 14-67785952-G-A is Benign according to our data. Variant chr14-67785952-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 385570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.083 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00139 (212/152254) while in subpopulation EAS AF = 0.00792 (41/5178). AF 95% confidence interval is 0.00665. There are 2 homozygotes in GnomAd4. There are 119 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015346.4. 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
	ZFYVE26	NM_015346.4	MANE Select	c.3210C>T	p.Pro1070Pro	synonymous	Exon 18 of 42	NP_056161.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE26	ENST00000347230.9	TSL:1 MANE Select	c.3210C>T	p.Pro1070Pro	synonymous	Exon 18 of 42	ENSP00000251119.5	Q68DK2-1
	ZFYVE26	ENST00000555452.1	TSL:1	c.3210C>T	p.Pro1070Pro	synonymous	Exon 18 of 35	ENSP00000450603.1	G3V2D8
	ZFYVE26	ENST00000554523.5	TSL:1	n.3347C>T		non_coding_transcript_exon	Exon 18 of 41

Frequencies

GnomAD3 genomes AF: 0.00139 AC: 211 AN: 152136 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00766

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00809

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00481 AC: 1210 AN: 251408 AF XY: 0.00389

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0259

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00837

Gnomad FIN exome AF: 0.00407

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.00134 AC: 1959 AN: 1461890 Hom.: 25 Cov.: 35 AF XY: 0.00124 AC XY: 902 AN XY: 727246

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.0238 AC: 1064 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.0110 AC: 436 AN: 39700

South Asian (SAS) AF: 0.000869 AC: 75 AN: 86258

European-Finnish (FIN) AF: 0.00401 AC: 214 AN: 53416

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000917 AC: 102 AN: 1112012

Other (OTH) AF: 0.000993 AC: 60 AN: 60396

GnomAD4 genome AF: 0.00139 AC: 212 AN: 152254 Hom.: 2 Cov.: 32 AF XY: 0.00160 AC XY: 119 AN XY: 74438

African (AFR) AF: 0.0000722 AC: 3 AN: 41532

American (AMR) AF: 0.00778 AC: 119 AN: 15294

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

East Asian (EAS) AF: 0.00792 AC: 41 AN: 5178

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00292 AC: 31 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68018

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000518 Hom.: 3

Bravo AF: 0.00254

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hereditary spastic paraplegia 15 (2)
-	-	1	Hereditary spastic paraplegia (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	9.0
DANN	Benign	0.65
PhyloP100		0.083
Mutation Taster		=97/3	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: rs7156492; hg19: chr14-68252669; COSMIC: COSV61328966;