17-81891535-G-A

Variant names:

• chr17-81891535-G-A
• rs1419634192
• NM_005782.4:c.46C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_005782.4(ALYREF):​c.46C>T​(p.Leu16Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,283,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: ALYREF NM_005782.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.38
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 17-81891535-G-A is Benign according to our data. Variant chr17-81891535-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3350262.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.38 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 16 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005782.4. 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
	ALYREF	NM_005782.4	MANE Select	c.46C>T	p.Leu16Leu	synonymous	Exon 1 of 6	NP_005773.3	E9PB61
	ANAPC11	NM_001289414.1		c.-75+684G>A		intron	N/A	NP_001276343.1	Q9NYG5-1
	ALYREF	NR_158770.1		n.53C>T		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALYREF	ENST00000505490.3	TSL:1 MANE Select	c.46C>T	p.Leu16Leu	synonymous	Exon 1 of 6	ENSP00000421592.2	E9PB61
	ALYREF	ENST00000864755.1		c.46C>T	p.Leu16Leu	synonymous	Exon 1 of 6	ENSP00000534814.1
	ANAPC11	ENST00000571570.5	TSL:3	c.-75+684G>A		intron	N/A	ENSP00000458143.1	Q9NYG5-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.000236 AC: 19 AN: 80500 AF XY: 0.000108

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00108

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000881

GnomAD4 exome AF: 0.0000125 AC: 16 AN: 1283626 Hom.: 0 Cov.: 31 AF XY: 0.00000790 AC XY: 5 AN XY: 633302

African (AFR) AF: 0.00 AC: 0 AN: 25540

American (AMR) AF: 0.000590 AC: 15 AN: 25422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21710

East Asian (EAS) AF: 0.00 AC: 0 AN: 25294

South Asian (SAS) AF: 0.00 AC: 0 AN: 72960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5282

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1024934

Other (OTH) AF: 0.0000193 AC: 1 AN: 51870

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ALYREF-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	11
DANN	Uncertain	0.98
PhyloP100		1.4
PromoterAI		0.0076	Neutral

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: rs1419634192; hg19: chr17-79849411;