5-151103620-G-A

Variant names:

• chr5-151103620-G-A
• rs1012456943
• NM_001155.5:c.1912C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001155.5(ANXA6):​c.1912C>T​(p.Arg638Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,611,690 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R638Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: ANXA6 NM_001155.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.85
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.1912C>T	p.Arg638Trp	missense	Exon 25 of 26	NP_001146.2	A0A0S2Z2Z6
	ANXA6	NM_001363114.2		c.1894C>T	p.Arg632Trp	missense	Exon 24 of 25	NP_001350043.1	A0A0S2Z377
	ANXA6	NM_001193544.2		c.1816C>T	p.Arg606Trp	missense	Exon 24 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.1912C>T	p.Arg638Trp	missense	Exon 25 of 26	ENSP00000346550.5	P08133-1
	ANXA6	ENST00000941434.1		c.2008C>T	p.Arg670Trp	missense	Exon 26 of 27	ENSP00000611493.1
	ANXA6	ENST00000935749.1		c.1990C>T	p.Arg664Trp	missense	Exon 24 of 25	ENSP00000605808.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000735 AC: 18 AN: 244824 AF XY: 0.0000452

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000472

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000564

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.0000199 AC: 29 AN: 1459514 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 725782

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.000338 AC: 15 AN: 44424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26050

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39572

South Asian (SAS) AF: 0.00 AC: 0 AN: 85642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1111020

Other (OTH) AF: 0.0000497 AC: 3 AN: 60314

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.39	T
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		2.8
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.69		Loss of disorder (P = 0.0899)
MVP		0.67
MPC		0.43
ClinPred		0.84	D
GERP RS		3.7
Varity_R		0.72
gMVP		0.80
Mutation Taster		=38/62	disease causing

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: rs1012456943; hg19: chr5-150483181; COSMIC: COSV62907753;