rs1214196580

Variant names:

• chr5-151117179-C-A
• NM_001155.5:c.1520G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-151117179-C-A
• chr5-151117179-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001155.5(ANXA6):​c.1520G>T​(p.Gly507Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000139 in 1,438,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ANXA6 NM_001155.5 missense, splice_region
• Scores: Splicing: ADA: 0.9767
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.60

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.766

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA6	NM_001155.5	c.1520G>T	p.Gly507Val	missense_variant, splice_region_variant	Exon 20 of 26	ENST00000354546.10	NP_001146.2
ANXA6	NM_001363114.2	c.1520G>T	p.Gly507Val	missense_variant, splice_region_variant	Exon 20 of 25		NP_001350043.1
ANXA6	NM_001193544.2	c.1424G>T	p.Gly475Val	missense_variant, splice_region_variant	Exon 19 of 25		NP_001180473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA6	ENST00000354546.10	c.1520G>T	p.Gly507Val	missense_variant, splice_region_variant	Exon 20 of 26	1	NM_001155.5	ENSP00000346550.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1438770 Hom.: 0 Cov.: 31 AF XY: 0.00000280 AC XY: 2 AN XY: 714848

Gnomad4 AFR exome AF: 0.0000615

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T;.;T;T
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.77	T;T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.77	D;D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.3	M;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.5	D;D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.015	D;D;D;D
Sift4G	Uncertain	0.038	D;D;D;D
Polyphen		1.0	D;.;.;D
Vest4		0.80
MutPred		0.58		Loss of disorder (P = 0.0224);.;.;.;
MVP		0.78
MPC		0.46
ClinPred		0.98	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.66
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.98
dbscSNV1_RF	Pathogenic	0.77
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: chr5-150496740;