10-73376133-C-G

Variant names:

• chr10-73376133-C-G
• rs73272348
• NM_001156.5:c.1363G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001156.5(ANXA7):​c.1363G>C​(p.Asp455His) variant causes a missense change. The variant allele was found at a frequency of 0.000252 in 1,603,896 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: ANXA7 NM_001156.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.04
• Publications: 2 publications found

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]

ENSG00000233144 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05788383).
• BP6: Variant 10-73376133-C-G is Benign according to our data. Variant chr10-73376133-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 716398.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA7	NM_001156.5	MANE Select	c.1363G>C	p.Asp455His	missense	Exon 13 of 13	NP_001147.1	P20073-2
	ANXA7	NM_004034.4		c.1429G>C	p.Asp477His	missense	Exon 14 of 14	NP_004025.1	P20073-1
	ANXA7	NM_001320880.2		c.1309G>C	p.Asp437His	missense	Exon 13 of 13	NP_001307809.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA7	ENST00000372921.10	TSL:1 MANE Select	c.1363G>C	p.Asp455His	missense	Exon 13 of 13	ENSP00000362012.4	P20073-2
	ANXA7	ENST00000372919.8	TSL:1	c.1429G>C	p.Asp477His	missense	Exon 14 of 14	ENSP00000362010.4	P20073-1
	ANXA7	ENST00000961271.1		c.1453G>C	p.Asp485His	missense	Exon 14 of 14	ENSP00000631330.1

Frequencies

GnomAD3 genomes AF: 0.00117 AC: 177 AN: 151726 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00390

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.000388 AC: 94 AN: 242494 AF XY: 0.000267

Gnomad AFR exome AF: 0.00446

Gnomad AMR exome AF: 0.000302

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000101

Gnomad OTH exome AF: 0.000336

GnomAD4 exome AF: 0.000157 AC: 228 AN: 1452064 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 97 AN XY: 721776

African (AFR) AF: 0.00447 AC: 148 AN: 33086

American (AMR) AF: 0.000275 AC: 12 AN: 43646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25916

East Asian (EAS) AF: 0.00 AC: 0 AN: 39408

South Asian (SAS) AF: 0.00 AC: 0 AN: 83194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53174

Middle Eastern (MID) AF: 0.000524 AC: 3 AN: 5728

European-Non Finnish (NFE) AF: 0.0000397 AC: 44 AN: 1107882

Other (OTH) AF: 0.000350 AC: 21 AN: 60030

GnomAD4 genome AF: 0.00116 AC: 176 AN: 151832 Hom.: 1 Cov.: 31 AF XY: 0.00105 AC XY: 78 AN XY: 74190

African (AFR) AF: 0.00389 AC: 161 AN: 41438

American (AMR) AF: 0.000328 AC: 5 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67978

Other (OTH) AF: 0.00237 AC: 5 AN: 2106

Alfa AF: 0.000218 Hom.: 0

Bravo AF: 0.00137

ESP6500AA AF: 0.00318 AC: 14

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000436 AC: 53

Asia WGS AF: 0.000577 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.67
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	2.0	M
PhyloP100		6.0
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.34
Sift	Benign	0.12	T
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.87
MVP		0.64
MPC		0.33
ClinPred		0.048	T
GERP RS		5.8
Varity_R		0.61
Mutation Taster		=61/39	polymorphism

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: rs73272348; hg19: chr10-75135891;