10-80157656-C-T

Variant names:

• chr10-80157656-C-T
• NM_145868.2:c.1443G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BP6_Moderate BP7 BS2_Supporting

The NM_145868.2(ANXA11):​c.1443G>A​(p.Leu481Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,536 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ANXA11 NM_145868.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13
• Publications: 0 publications found

Genes affected

ANXA11 (HGNC:535): (annexin A11) This gene encodes a member of the annexin family, a group of calcium-dependent phospholipid-binding proteins. Annexins have unique N-terminal domains and conserved C-terminal domains, which contain calcium-dependent phospholipid-binding sites. The encoded protein is a 56-kD antigen recognized by sera from patients with various autoimmune diseases. Several transcript variants encoding two different isoforms have been identified. [provided by RefSeq, Dec 2015]

ANXA11 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis type 23

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• inclusion body myopathy and brain white matter abnormalities

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.124).
• BP6: Variant 10-80157656-C-T is Benign according to our data. Variant chr10-80157656-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1966438.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.13 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA11	NM_145868.2	c.1443G>A	p.Leu481Leu	synonymous_variant	Exon 15 of 16	ENST00000422982.8	NP_665875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA11	ENST00000422982.8	c.1443G>A	p.Leu481Leu	synonymous_variant	Exon 15 of 16	1	NM_145868.2	ENSP00000404412.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461536 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727034

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111766

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 17, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr10-81917412;