chr4-168177938-C-G

Variant names:

• chr4-168177938-C-G
• rs114585401
• NM_007193.5:c.583C>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_007193.5(ANXA10):​c.583C>G​(p.Leu195Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000813 in 1,613,676 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (9 hom.)
• Consequence: ANXA10 NM_007193.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.322
• Publications: 0 publications found

Genes affected

ANXA10 (HGNC:534): (annexin A10) This gene encodes a member of the annexin family. Members of this calcium-dependent phospholipid-binding protein family play a role in the regulation of cellular growth and in signal transduction pathways. The function of this gene has not yet been determined. [provided by RefSeq, Jul 2008]

ENSG00000287188 (HGNC:58907):

LOC105377524 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0091920495).
• BP6: Variant 4-168177938-C-G is Benign according to our data. Variant chr4-168177938-C-G is described in ClinVar as Benign. ClinVar VariationId is 790558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007193.5. 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
	ANXA10	NM_007193.5	MANE Select	c.583C>G	p.Leu195Val	missense	Exon 8 of 12	NP_009124.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA10	ENST00000359299.8	TSL:1 MANE Select	c.583C>G	p.Leu195Val	missense	Exon 8 of 12	ENSP00000352248.3	Q9UJ72
	ANXA10	ENST00000507278.5	TSL:1	n.246C>G		non_coding_transcript_exon	Exon 3 of 7
	ANXA10	ENST00000503003.1	TSL:2	n.189C>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.00440 AC: 669 AN: 152132 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00113 AC: 284 AN: 251346 AF XY: 0.000876

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.000814

GnomAD4 exome AF: 0.000439 AC: 642 AN: 1461426 Hom.: 9 Cov.: 32 AF XY: 0.000388 AC XY: 282 AN XY: 727022

African (AFR) AF: 0.0149 AC: 500 AN: 33474

American (AMR) AF: 0.000962 AC: 43 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000891 AC: 5 AN: 5614

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1111794

Other (OTH) AF: 0.000977 AC: 59 AN: 60360

GnomAD4 genome AF: 0.00440 AC: 670 AN: 152250 Hom.: 3 Cov.: 32 AF XY: 0.00424 AC XY: 316 AN XY: 74450

African (AFR) AF: 0.0148 AC: 614 AN: 41556

American (AMR) AF: 0.00262 AC: 40 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68006

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.000581 Hom.: 1

Bravo AF: 0.00487

ESP6500AA AF: 0.0141 AC: 62

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00133 AC: 162

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.0092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.32
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.052
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.17	B
Vest4		0.55
MVP		0.092
MPC		0.17
ClinPred		0.077	T
GERP RS		3.0
Varity_R		0.25
gMVP		0.30
Mutation Taster		=100/0	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: rs114585401; hg19: chr4-169099089;