11-65086586-G-T

Variant names:

• chr11-65086586-G-T
• rs747733761
• NM_006782.4:c.386G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006782.4(ZFPL1):​c.386G>T​(p.Arg129Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R129Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFPL1 NM_006782.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.90
• Publications: 0 publications found

Genes affected

ZFPL1 (HGNC:12868): (zinc finger protein like 1) Predicted to enable metal ion binding activity. Predicted to be involved in vesicle-mediated transport. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

TMEM262 (HGNC:49389): (transmembrane protein 262) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.849

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006782.4. 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
	ZFPL1	NM_006782.4	MANE Select	c.386G>T	p.Arg129Leu	missense	Exon 4 of 8	NP_006773.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPL1	ENST00000294258.8	TSL:1 MANE Select	c.386G>T	p.Arg129Leu	missense	Exon 4 of 8	ENSP00000294258.3	O95159
	ZFPL1	ENST00000890495.1		c.386G>T	p.Arg129Leu	missense	Exon 4 of 8	ENSP00000560554.1
	ZFPL1	ENST00000532200.1	TSL:2	c.386G>T	p.Arg129Leu	missense	Exon 3 of 5	ENSP00000437090.1	E9PNY1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.068	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.31	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		8.9
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Uncertain	0.57
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.63		Loss of MoRF binding (P = 0.0316)
MVP		0.37
MPC		0.91
ClinPred		1.0	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.84
gMVP		0.81
Mutation Taster		=8/92	disease causing

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: rs747733761; hg19: chr11-64854058; COSMIC: COSV51869999; COSMIC: COSV51869999;