Genetic Variant ANXA6:p.Thr621Ser (chr5-151103671-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001155.5(ANXA6):c.1861A>T(p.Thr621Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T621A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ANXA6
NM_001155.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.50

Publications

0 publications found

Variant links:

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]

ANXA6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37177336).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANXA6	NM_001155.5	MANE Select	c.1861A>T	p.Thr621Ser	missense	Exon 25 of 26	NP_001146.2	A0A0S2Z2Z6
ANXA6	NM_001363114.2		c.1843A>T	p.Thr615Ser	missense	Exon 24 of 25	NP_001350043.1	A0A0S2Z377
ANXA6	NM_001193544.2		c.1765A>T	p.Thr589Ser	missense	Exon 24 of 25	NP_001180473.1	P08133-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANXA6	ENST00000354546.10	TSL:1 MANE Select	c.1861A>T	p.Thr621Ser	missense	Exon 25 of 26	ENSP00000346550.5	P08133-1
ANXA6	ENST00000941434.1		c.1957A>T	p.Thr653Ser	missense	Exon 26 of 27	ENSP00000611493.1
ANXA6	ENST00000935749.1		c.1939A>T	p.Thr647Ser	missense	Exon 24 of 25	ENSP00000605808.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0097

MetaRNN

Benign

0.37

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

3.5

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.62

REVEL

Benign

0.12

Sift

Uncertain

0.0070

Sift4G

Benign

0.20

Polyphen

0.60

Vest4

0.38

MutPred

0.64

Gain of disorder (P = 0.051)

MVP

0.62

MPC

0.26

ClinPred

0.84

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.46

gMVP

0.30

Mutation Taster

=71/29

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over