14-67798150-A-G

Variant names:

• chr14-67798150-A-G
• rs12891164
• NM_015346.4:c.2112T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015346.4(ZFYVE26):​c.2112T>C​(p.Pro704Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 1,613,782 control chromosomes in the GnomAD database, including 366,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (36069 hom., cov: 31)
  • Exomes 𝑓: 0.67 (330359 hom.)
• Consequence: ZFYVE26 NM_015346.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0810
• Publications: 28 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 14-67798150-A-G is Benign according to our data. Variant chr14-67798150-A-G is described in ClinVar as Benign. ClinVar VariationId is 695138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.081 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 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.2112T>C	p.Pro704Pro	synonymous	Exon 11 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.2112T>C	p.Pro704Pro	synonymous	Exon 11 of 42	ENSP00000251119.5	Q68DK2-1
	ZFYVE26	ENST00000555452.1	TSL:1	c.2112T>C	p.Pro704Pro	synonymous	Exon 11 of 35	ENSP00000450603.1	G3V2D8
	ZFYVE26	ENST00000554523.5	TSL:1	n.2249T>C		non_coding_transcript_exon	Exon 11 of 41

Frequencies

GnomAD3 genomes AF: 0.685 AC: 103982 AN: 151892 Hom.: 36044 Cov.: 31

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.678

GnomAD2 exomes AF: 0.715 AC: 179736 AN: 251258 AF XY: 0.713

Gnomad AFR exome AF: 0.684

Gnomad AMR exome AF: 0.803

Gnomad ASJ exome AF: 0.569

Gnomad EAS exome AF: 0.978

Gnomad FIN exome AF: 0.717

Gnomad NFE exome AF: 0.648

Gnomad OTH exome AF: 0.673

GnomAD4 exome AF: 0.668 AC: 977085 AN: 1461772 Hom.: 330359 Cov.: 80 AF XY: 0.671 AC XY: 487842 AN XY: 727170

African (AFR) AF: 0.680 AC: 22769 AN: 33480

American (AMR) AF: 0.793 AC: 35472 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 15115 AN: 26132

East Asian (EAS) AF: 0.976 AC: 38731 AN: 39698

South Asian (SAS) AF: 0.779 AC: 67156 AN: 86254

European-Finnish (FIN) AF: 0.716 AC: 38247 AN: 53404

Middle Eastern (MID) AF: 0.642 AC: 3701 AN: 5768

European-Non Finnish (NFE) AF: 0.643 AC: 715178 AN: 1111922

Other (OTH) AF: 0.674 AC: 40716 AN: 60396

GnomAD4 genome AF: 0.685 AC: 104055 AN: 152010 Hom.: 36069 Cov.: 31 AF XY: 0.693 AC XY: 51461 AN XY: 74306

African (AFR) AF: 0.683 AC: 28312 AN: 41432

American (AMR) AF: 0.747 AC: 11401 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1958 AN: 3470

East Asian (EAS) AF: 0.977 AC: 5065 AN: 5184

South Asian (SAS) AF: 0.773 AC: 3720 AN: 4812

European-Finnish (FIN) AF: 0.721 AC: 7629 AN: 10576

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.644 AC: 43779 AN: 67952

Other (OTH) AF: 0.682 AC: 1440 AN: 2110

Alfa AF: 0.655 Hom.: 134450

Bravo AF: 0.686

Asia WGS AF: 0.848 AC: 2948 AN: 3478

EpiCase AF: 0.634

EpiControl AF: 0.639

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.73
DANN	Benign	0.42
PhyloP100		0.081
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: rs12891164; hg19: chr14-68264867; COSMIC: COSV108188348; COSMIC: COSV108188348;