rs559011700

Variant names:

• chr17-81891576-G-A
• NM_005782.4:c.5C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-81891576-G-A
• chr17-81891576-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_005782.4(ALYREF):​c.5C>T​(p.Pro2Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000156 in 1,284,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign 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. P2H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: ALYREF NM_005782.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17

Genes affected

ALYREF (HGNC:19071): (Aly/REF export factor) The protein encoded by this gene is a heat stable, nuclear protein and functions as a molecular chaperone. It is thought to regulate dimerization, DNA binding, and transcriptional activity of basic region-leucine zipper (bZIP) proteins. [provided by RefSeq, Jul 2008]

ANAPC11 (HGNC:14452): (anaphase promoting complex subunit 11) Enables cullin family protein binding activity and ubiquitin-ubiquitin ligase activity. Contributes to ubiquitin-protein transferase activity. Involved in protein K11-linked ubiquitination. Located in nucleolus and nucleoplasm. Part of anaphase-promoting complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a modified_residue N-acetylalanine (size 0) in uniprot entity THOC4_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12822458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALYREF	NM_005782.4	c.5C>T	p.Pro2Leu	missense_variant	Exon 1 of 6	ENST00000505490.3	NP_005773.3
ANAPC11	NM_001002248.3	c.-340G>A		upstream_gene_variant		ENST00000344877.10	NP_001002248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALYREF	ENST00000505490.3	c.5C>T	p.Pro2Leu	missense_variant	Exon 1 of 6	1	NM_005782.4	ENSP00000421592.2
ANAPC11	ENST00000344877.10	c.-340G>A		upstream_gene_variant		1	NM_001002248.3	ENSP00000339695.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000156 AC: 2 AN: 1284088 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 633348

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000137

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.75e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.030
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.11	B
Vest4		0.28
MutPred		0.14		Loss of catalytic residue at P2 (P = 0.0035);
MVP		0.10
MPC		1.2
ClinPred		0.92	D
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
gMVP		0.26

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-79849452;