chr5-151117154-G-A

Variant names:

• chr5-151117154-G-A
• rs578098716
• NM_001155.5:c.1545C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001155.5(ANXA6):​c.1545C>T​(p.Asn515Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,374 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ANXA6 NM_001155.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.739
• Publications: 0 publications found

Genes affected

ANXA6 (HGNC:544): (annexin A6) Annexin VI belongs to a family of calcium-dependent membrane and phospholipid binding proteins. Several members of the annexin family have been implicated in membrane-related events along exocytotic and endocytotic pathways. The annexin VI gene is approximately 60 kbp long and contains 26 exons. It encodes a protein of about 68 kDa that consists of eight 68-amino acid repeats separated by linking sequences of variable lengths. It is highly similar to human annexins I and II sequences, each of which contain four such repeats. Annexin VI has been implicated in mediating the endosome aggregation and vesicle fusion in secreting epithelia during exocytosis. Alternatively spliced transcript variants have been described. [provided by RefSeq, Aug 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=0.739 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001155.5. 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
	ANXA6	NM_001155.5	MANE Select	c.1545C>T	p.Asn515Asn	synonymous	Exon 20 of 26	NP_001146.2	A0A0S2Z2Z6
	ANXA6	NM_001363114.2		c.1545C>T	p.Asn515Asn	synonymous	Exon 20 of 25	NP_001350043.1	A0A0S2Z377
	ANXA6	NM_001193544.2		c.1449C>T	p.Asn483Asn	synonymous	Exon 19 of 25	NP_001180473.1	P08133-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA6	ENST00000354546.10	TSL:1 MANE Select	c.1545C>T	p.Asn515Asn	synonymous	Exon 20 of 26	ENSP00000346550.5	P08133-1
	ANXA6	ENST00000941434.1		c.1641C>T	p.Asn547Asn	synonymous	Exon 21 of 27	ENSP00000611493.1
	ANXA6	ENST00000935749.1		c.1623C>T	p.Asn541Asn	synonymous	Exon 19 of 25	ENSP00000605808.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442374 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 717140

African (AFR) AF: 0.00 AC: 0 AN: 32566

American (AMR) AF: 0.00 AC: 0 AN: 42992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25600

East Asian (EAS) AF: 0.00 AC: 0 AN: 37826

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53046

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101134

Other (OTH) AF: 0.00 AC: 0 AN: 59428

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.6
DANN	Benign	0.72
PhyloP100		0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs578098716; hg19: chr5-150496715;