chr10-73383182-A-C

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001156.5(ANXA7):c.911T>G(p.Met304Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. M304T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ANXA7
NM_001156.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.18

Publications

2 publications found

Variant links:

Genes affected

ANXA7 (HGNC:545): (annexin A7) Annexin VII is a member of the annexin family of calcium-dependent phospholipid binding proteins.The Annexin VII gene contains 14 exons and spans approximately 34 kb of DNA. An alternatively spliced cassette exon results in two mRNA transcripts of 2.0 and 2.4 kb which are predicted to generate two protein isoforms differing in their N-terminal domain. The alternative splicing event is tissue specific and the mRNA containing the cassette exon is prevalent in brain, heart and skeletal muscle. The transcripts also differ in their 3'-non coding regions by the use of two alternative poly(A) signals. Annexin VII encodes a protein with a molecular weight of approximately 51 kDa with a unique, highly hydrophobic N-terminal domain of 167 amino acids and a conserved C-terminal region of 299 amino acids. The latter domain is composed of alternating hydrophobic and hydrophilic segments. Structural analysis of the protein suggests that Annexin VII is a membrane binding protein with diverse properties, including voltage-sensitive calcium channel activity, ion selectivity and membrane fusion. [provided by RefSeq, Jul 2008]

ANXA7 links:

ENSG00000233144 (HGNC:):

ENSG00000233144 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.963

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001156.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANXA7	NM_001156.5	MANE Select	c.911T>G	p.Met304Arg	missense	Exon 9 of 13	NP_001147.1	P20073-2
ANXA7	NM_004034.4		c.977T>G	p.Met326Arg	missense	Exon 10 of 14	NP_004025.1	P20073-1
ANXA7	NM_001320880.2		c.857T>G	p.Met286Arg	missense	Exon 9 of 13	NP_001307809.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANXA7	ENST00000372921.10	TSL:1 MANE Select	c.911T>G	p.Met304Arg	missense	Exon 9 of 13	ENSP00000362012.4	P20073-2
ANXA7	ENST00000372919.8	TSL:1	c.977T>G	p.Met326Arg	missense	Exon 10 of 14	ENSP00000362010.4	P20073-1
ANXA7	ENST00000961271.1		c.1001T>G	p.Met334Arg	missense	Exon 10 of 14	ENSP00000631330.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000799

AC:

AN:

250386

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460090

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726104

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33446

American (AMR)

AF:

0.00

AC:

AN:

44524

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.0000349

AC:

AN:

86014

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110900

Other (OTH)

AF:

0.00

AC:

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.026

MetaRNN

Pathogenic

0.96

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.8

PhyloP100

7.2

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.96

MutPred

0.88

Gain of disorder (P = 0.0339)

MVP

0.81

MPC

0.32

ClinPred

0.97

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.93

Mutation Taster

=51/49

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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