rs79622405

Variant names:

• chr10-80154555-G-A
• rs79622405
• NM_145868.2:c.*1298C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145868.2(ANXA11):​c.*1298C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 152,272 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.020 (103 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANXA11 NM_145868.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0677 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145868.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA11	NM_145868.2	MANE Select	c.*1298C>T		3_prime_UTR	Exon 16 of 16	NP_665875.1
	ANXA11	NM_001157.3		c.*1298C>T		3_prime_UTR	Exon 15 of 15	NP_001148.1
	ANXA11	NM_001278407.2		c.*1298C>T		3_prime_UTR	Exon 17 of 17	NP_001265336.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA11	ENST00000422982.8	TSL:1 MANE Select	c.*1298C>T		3_prime_UTR	Exon 16 of 16	ENSP00000404412.2
	ANXA11	ENST00000372231.7	TSL:1	c.*1298C>T		3_prime_UTR	Exon 15 of 15	ENSP00000361305.3
	ANXA11	ENST00000438331.5	TSL:1	c.*1298C>T		3_prime_UTR	Exon 17 of 17	ENSP00000398610.1

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3043 AN: 152154 Hom.: 102 Cov.: 32

Gnomad AFR AF: 0.0697

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0163

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 20

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 24

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0201 AC: 3057 AN: 152272 Hom.: 103 Cov.: 32 AF XY: 0.0197 AC XY: 1464 AN XY: 74456

African (AFR) AF: 0.0698 AC: 2900 AN: 41544

American (AMR) AF: 0.00647 AC: 99 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68022

Other (OTH) AF: 0.0161 AC: 34 AN: 2114

Alfa AF: 0.0190 Hom.: 12

Bravo AF: 0.0224

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.84
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism

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: rs79622405; hg19: chr10-81914311;