11-65085202-G-A

Variant names:

• chr11-65085202-G-A
• rs377164955
• NM_006782.4:c.190G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006782.4(ZFPL1):​c.190G>A​(p.Glu64Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. E64Q) 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: 6.33
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.190G>A	p.Glu64Lys	missense	Exon 3 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.190G>A	p.Glu64Lys	missense	Exon 3 of 8	ENSP00000294258.3	O95159
	ZFPL1	ENST00000533216.1	TSL:1	n.335G>A		non_coding_transcript_exon	Exon 3 of 3
	ZFPL1	ENST00000890495.1		c.190G>A	p.Glu64Lys	missense	Exon 3 of 8	ENSP00000560554.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.9	L
PhyloP100		6.3
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.028	D
Polyphen		0.36	B
Vest4		0.54
MutPred		0.42		Gain of MoRF binding (P = 0.0702)
MVP		0.59
MPC		0.42
ClinPred		0.99	D
GERP RS		4.7
PromoterAI		0.021	Neutral
Varity_R		0.34
gMVP		0.63
Mutation Taster		=47/53	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: rs377164955; hg19: chr11-64852674;