NM_001155.5:c.1720G>C

Variant names:

• chr5-151108515-C-G
• rs547473117
• NM_001155.5:c.1720G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001155.5(ANXA6):​c.1720G>C​(p.Val574Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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)
• Consequence: ANXA6 NM_001155.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3879928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA6	NM_001155.5	c.1720G>C	p.Val574Leu	missense_variant	Exon 23 of 26	ENST00000354546.10	NP_001146.2
ANXA6	NM_001363114.2	c.1702G>C	p.Val568Leu	missense_variant	Exon 22 of 25		NP_001350043.1
ANXA6	NM_001193544.2	c.1624G>C	p.Val542Leu	missense_variant	Exon 22 of 25		NP_001180473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA6	ENST00000354546.10	c.1720G>C	p.Val574Leu	missense_variant	Exon 23 of 26	1	NM_001155.5	ENSP00000346550.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.10	T;.;T;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	-0.11	N;.;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.37	N;N;N;N
REVEL	Benign	0.045
Sift	Benign	0.092	T;T;T;T
Sift4G	Benign	0.54	T;T;T;T
Polyphen		0.018	B;.;.;B
Vest4		0.56
MutPred		0.68		Loss of helix (P = 0.1299);.;.;.;
MVP		0.56
MPC		0.078
ClinPred		0.48	T
GERP RS		1.8
Varity_R		0.061
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs547473117; hg19: chr5-150488076;