chr10-97753138-G-T

Position:

• chr10-97753138-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001385875.1(ZFYVE27):​c.998G>T​(p.Arg333Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZFYVE27 NM_001385875.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.75

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34381777).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFYVE27	NM_001385875.1	c.998G>T	p.Arg333Leu	missense_variant	10/13	ENST00000684270.1	NP_001372804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFYVE27	ENST00000684270.1	c.998G>T	p.Arg333Leu	missense_variant	10/13		NM_001385875.1	ENSP00000506975.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459920 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 726028

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	.;.;.;.;T;.;.
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.34	T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.3	.;.;.;.;M;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.4	D;D;D;D;D;.;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D;D;D;D;D;.;D
Sift4G	Uncertain	0.015	D;D;D;D;D;D;D
Polyphen		0.88, 0.36, 0.71, 0.68	.;.;.;P;B;P;P
Vest4		0.53
MutPred		0.42		.;.;.;.;Loss of MoRF binding (P = 0.0199);.;.;
MVP		0.62
ClinPred		0.99	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.31
gMVP		0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs370222554; hg19: chr10-99512895;