10-97738556-C-T

Position:

• chr10-97738556-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001385875.1(ZFYVE27):​c.79C>T​(p.Pro27Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 32)
• Consequence: ZFYVE27 NM_001385875.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046761364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFYVE27	NM_001385875.1	c.79C>T	p.Pro27Ser	missense_variant	2/13	ENST00000684270.1	NP_001372804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFYVE27	ENST00000684270.1	c.79C>T	p.Pro27Ser	missense_variant	2/13		NM_001385875.1	ENSP00000506975.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251490 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135916

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	.;.;.;T;.;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.78	T;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.047	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L;L;L;L;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.1	N;N;N;N;.;N
REVEL	Benign	0.017
Sift	Benign	0.063	T;D;D;T;.;T
Sift4G	Benign	0.15	T;D;T;T;T;T
Polyphen		0.0, 0.0010	.;.;B;B;B;B
Vest4		0.12
MutPred		0.23		Gain of phosphorylation at P27 (P = 0.017);Gain of phosphorylation at P27 (P = 0.017);Gain of phosphorylation at P27 (P = 0.017);Gain of phosphorylation at P27 (P = 0.017);Gain of phosphorylation at P27 (P = 0.017);Gain of phosphorylation at P27 (P = 0.017);
MVP		0.099
ClinPred		0.54	D
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.073
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34979921; hg19: chr10-99498313;