chr11-65085167-A-T

Variant names:

• chr11-65085167-A-T
• rs774361524
• NM_006782.4:c.155A>T

Variant summary

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

The NM_006782.4(ZFPL1):​c.155A>T​(p.Asn52Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. N52S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZFPL1 NM_006782.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.78
• 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.155A>T	p.Asn52Ile	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.155A>T	p.Asn52Ile	missense	Exon 3 of 8	ENSP00000294258.3	O95159
	ZFPL1	ENST00000533216.1	TSL:1	n.300A>T		non_coding_transcript_exon	Exon 3 of 3
	ZFPL1	ENST00000890495.1		c.155A>T	p.Asn52Ile	missense	Exon 3 of 8	ENSP00000560554.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	22
DANN	Benign	0.87
DEOGEN2	Benign	0.045	T
Eigen	Benign	0.061
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.8
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.54
Sift	Benign	0.36	T
Sift4G	Benign	0.26	T
Polyphen		0.36	B
Vest4		0.81
MutPred		0.50		Loss of loop (P = 0.0603)
MVP		0.34
MPC		0.37
ClinPred		0.76	D
GERP RS		3.8
PromoterAI		-0.014	Neutral
Varity_R		0.31
gMVP		0.67
Mutation Taster		=32/68	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: rs774361524; hg19: chr11-64852639;