rs249038

Variant names:

• chr5-80449650-A-G
• rs249038
• NM_001284236.3:c.3163A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-80449650-A-G
• chr5-80449650-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001284236.3(ZFYVE16):​c.3163A>G​(p.Ser1055Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 1,609,120 control chromosomes in the GnomAD database, including 693,829 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.87 (58962 hom., cov: 32)
  • Exomes 𝑓: 0.93 (634867 hom.)
• Consequence: ZFYVE16 NM_001284236.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 36 publications found

Genes affected

ZFYVE16 (HGNC:20756): (zinc finger FYVE-type containing 16) This gene encodes an endosomal protein that belongs to the FYVE zinc finger family of proteins. The encoded protein is thought to regulate membrane trafficking in the endosome. This protein functions as a scaffold protein in the transforming growth factor-beta signaling pathway and is involved in positive and negative feedback regulation of the bone morphogenetic protein signaling pathway. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

FAM151B-DT (HGNC:55578): (FAM151B divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1923908E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284236.3. 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
	ZFYVE16	NM_001284236.3	MANE Select	c.3163A>G	p.Ser1055Gly	missense	Exon 9 of 19	NP_001271165.2	Q7Z3T8-1
	ZFYVE16	NM_001105251.4		c.3163A>G	p.Ser1055Gly	missense	Exon 9 of 19	NP_001098721.2	Q7Z3T8-1
	ZFYVE16	NM_001349434.2		c.3163A>G	p.Ser1055Gly	missense	Exon 9 of 19	NP_001336363.2	Q7Z3T8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE16	ENST00000505560.5	TSL:1 MANE Select	c.3163A>G	p.Ser1055Gly	missense	Exon 9 of 19	ENSP00000426848.1	Q7Z3T8-1
	ZFYVE16	ENST00000338008.9	TSL:1	c.3163A>G	p.Ser1055Gly	missense	Exon 8 of 18	ENSP00000337159.5	Q7Z3T8-1
	ZFYVE16	ENST00000510158.5	TSL:1	c.3163A>G	p.Ser1055Gly	missense	Exon 9 of 19	ENSP00000423663.1	Q7Z3T8-1

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133038 AN: 152052 Hom.: 58929 Cov.: 32

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.943

Gnomad OTH AF: 0.879

GnomAD2 exomes AF: 0.914 AC: 225760 AN: 246940 AF XY: 0.914

Gnomad AFR exome AF: 0.707

Gnomad AMR exome AF: 0.954

Gnomad ASJ exome AF: 0.946

Gnomad EAS exome AF: 0.930

Gnomad FIN exome AF: 0.923

Gnomad NFE exome AF: 0.941

Gnomad OTH exome AF: 0.922

GnomAD4 exome AF: 0.932 AC: 1358538 AN: 1456950 Hom.: 634867 Cov.: 38 AF XY: 0.930 AC XY: 674112 AN XY: 724862

African (AFR) AF: 0.706 AC: 23388 AN: 33120

American (AMR) AF: 0.951 AC: 41628 AN: 43770

Ashkenazi Jewish (ASJ) AF: 0.944 AC: 24571 AN: 26032

East Asian (EAS) AF: 0.948 AC: 37220 AN: 39260

South Asian (SAS) AF: 0.852 AC: 72731 AN: 85408

European-Finnish (FIN) AF: 0.921 AC: 49138 AN: 53364

Middle Eastern (MID) AF: 0.875 AC: 5010 AN: 5726

European-Non Finnish (NFE) AF: 0.946 AC: 1049942 AN: 1110104

Other (OTH) AF: 0.913 AC: 54910 AN: 60166

GnomAD4 genome AF: 0.875 AC: 133122 AN: 152170 Hom.: 58962 Cov.: 32 AF XY: 0.874 AC XY: 65038 AN XY: 74384

African (AFR) AF: 0.721 AC: 29936 AN: 41494

American (AMR) AF: 0.929 AC: 14198 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 3267 AN: 3472

East Asian (EAS) AF: 0.922 AC: 4786 AN: 5192

South Asian (SAS) AF: 0.849 AC: 4093 AN: 4822

European-Finnish (FIN) AF: 0.916 AC: 9702 AN: 10590

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.943 AC: 64124 AN: 67996

Other (OTH) AF: 0.878 AC: 1858 AN: 2116

Alfa AF: 0.919 Hom.: 213605

Bravo AF: 0.870

TwinsUK AF: 0.947 AC: 3510

ALSPAC AF: 0.947 AC: 3650

ESP6500AA AF: 0.719 AC: 3166

ESP6500EA AF: 0.943 AC: 8108

ExAC AF: 0.909 AC: 110373

Asia WGS AF: 0.888 AC: 3086 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.2
DANN	Benign	0.16
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.047	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.2	N
PhyloP100		2.5
PrimateAI	Benign	0.26	T
PROVEAN	Benign	4.1	N
REVEL	Benign	0.097
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.0070
MPC		0.043
ClinPred		0.0052	T
GERP RS		5.0
Varity_R		0.027
gMVP		0.036
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs249038; hg19: chr5-79745469; COSMIC: COSV62014988; COSMIC: COSV62014988;