rs35106153

Variant names:

• chr14-67751061-A-G
• rs35106153
• NM_015346.4:c.7407T>C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_015346.4(ZFYVE26):​c.7407T>C​(p.Asp2469Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00315 in 1,614,180 control chromosomes in the GnomAD database, including 161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (89 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (72 hom.)
• Consequence: ZFYVE26 NM_015346.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.814
• Publications: 0 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]

RN7SL213P (HGNC:46229): (RNA, 7SL, cytoplasmic 213, pseudogene)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 14-67751061-A-G is Benign according to our data. Variant chr14-67751061-A-G is described in ClinVar as Benign. ClinVar VariationId is 241059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.814 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

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.7407T>C	p.Asp2469Asp	synonymous	Exon 41 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.7407T>C	p.Asp2469Asp	synonymous	Exon 41 of 42	ENSP00000251119.5	Q68DK2-1
	ZFYVE26	ENST00000557306.1	TSL:1	c.945T>C	p.Asp315Asp	synonymous	Exon 7 of 7	ENSP00000452142.1	A0A2H2FF08
	ZFYVE26	ENST00000554523.5	TSL:1	n.8162T>C		non_coding_transcript_exon	Exon 40 of 41

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2624 AN: 152178 Hom.: 89 Cov.: 32

Gnomad AFR AF: 0.0600

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00475 AC: 1194 AN: 251466 AF XY: 0.00365

Gnomad AFR exome AF: 0.0654

Gnomad AMR exome AF: 0.00292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00168 AC: 2458 AN: 1461884 Hom.: 72 Cov.: 30 AF XY: 0.00144 AC XY: 1048 AN XY: 727246

African (AFR) AF: 0.0594 AC: 1988 AN: 33478

American (AMR) AF: 0.00342 AC: 153 AN: 44724

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

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

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0000638 AC: 71 AN: 1112010

Other (OTH) AF: 0.00392 AC: 237 AN: 60396

GnomAD4 genome AF: 0.0173 AC: 2631 AN: 152296 Hom.: 89 Cov.: 32 AF XY: 0.0166 AC XY: 1238 AN XY: 74488

African (AFR) AF: 0.0600 AC: 2491 AN: 41544

American (AMR) AF: 0.00634 AC: 97 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68018

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.00859 Hom.: 27

Bravo AF: 0.0201

Asia WGS AF: 0.00462 AC: 17 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	6.5
DANN	Benign	0.81
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

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: rs35106153; hg19: chr14-68217778;