chr10-46390897-C-T

Variant names:

• chr10-46390897-C-T
• rs184551877
• NM_001098845.3:c.951C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001098845.3(ANXA8L1):​c.951C>T​(p.Asn317Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00373 in 1,383,090 control chromosomes in the GnomAD database, including 1,110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (36 hom., cov: 15)
  • Exomes 𝑓: 0.0039 (1074 hom.)
• Consequence: ANXA8L1 NM_001098845.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.94
• Publications: 0 publications found

Genes affected

ANXA8L1 (HGNC:23334): (annexin A8 like 1) This gene encodes a member of the annexin family of evolutionarily conserved Ca2+ and phospholipid binding proteins. The encoded protein may function as an an anticoagulant that indirectly inhibits the thromboplastin-specific complex. Overexpression of this gene has been associated with acute myelocytic leukemia. A highly similar duplicated copy of this gene is found in close proximity on the long arm of chromosome 10. [provided by RefSeq, Apr 2014]

ENSG00000285402 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 10-46390897-C-T is Benign according to our data. Variant chr10-46390897-C-T is described in ClinVar as Benign. ClinVar VariationId is 2640434.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.94 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 36 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098845.3. 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
	ANXA8L1	NM_001098845.3	MANE Select	c.951C>T	p.Asn317Asn	synonymous	Exon 12 of 12	NP_001092315.2	Q5VT79-1
	ANXA8L1	NM_001278924.2		c.798C>T	p.Asn266Asn	synonymous	Exon 9 of 9	NP_001265853.1	Q5VT79-2
	ANXA8L1	NM_001278923.2		c.780C>T	p.Asn260Asn	synonymous	Exon 10 of 10	NP_001265852.1	B4DTF2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA8L1	ENST00000619162.5	TSL:1 MANE Select	c.951C>T	p.Asn317Asn	synonymous	Exon 12 of 12	ENSP00000480221.1	Q5VT79-1
	ANXA8L1	ENST00000622769.4	TSL:1	c.798C>T	p.Asn266Asn	synonymous	Exon 9 of 9	ENSP00000483608.1	Q5VT79-2
	ANXA8L1	ENST00000584982.7	TSL:2	c.1065C>T	p.Asn355Asn	synonymous	Exon 12 of 12	ENSP00000462716.2	A0A075B752

Frequencies

GnomAD3 genomes AF: 0.00226 AC: 235 AN: 103994 Hom.: 36 Cov.: 15

Gnomad AFR AF: 0.000499

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00103

Gnomad ASJ AF: 0.00539

Gnomad EAS AF: 0.000202

Gnomad SAS AF: 0.000285

Gnomad FIN AF: 0.000594

Gnomad MID AF: 0.0126

Gnomad NFE AF: 0.00393

Gnomad OTH AF: 0.00217

GnomAD2 exomes AF: 0.00527 AC: 1162 AN: 220414 AF XY: 0.00555

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.00284

Gnomad ASJ exome AF: 0.0366

Gnomad EAS exome AF: 0.000165

Gnomad FIN exome AF: 0.00136

Gnomad NFE exome AF: 0.00664

Gnomad OTH exome AF: 0.00808

GnomAD4 exome AF: 0.00385 AC: 4929 AN: 1278982 Hom.: 1074 Cov.: 30 AF XY: 0.00383 AC XY: 2430 AN XY: 634486

African (AFR) AF: 0.000417 AC: 13 AN: 31150

American (AMR) AF: 0.00154 AC: 62 AN: 40158

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 374 AN: 21226

East Asian (EAS) AF: 0.0000509 AC: 2 AN: 39272

South Asian (SAS) AF: 0.00114 AC: 89 AN: 78102

European-Finnish (FIN) AF: 0.00105 AC: 45 AN: 42976

Middle Eastern (MID) AF: 0.00529 AC: 19 AN: 3594

European-Non Finnish (NFE) AF: 0.00423 AC: 4099 AN: 970140

Other (OTH) AF: 0.00432 AC: 226 AN: 52364

GnomAD4 genome AF: 0.00226 AC: 235 AN: 104108 Hom.: 36 Cov.: 15 AF XY: 0.00205 AC XY: 103 AN XY: 50346

African (AFR) AF: 0.000497 AC: 13 AN: 26154

American (AMR) AF: 0.00103 AC: 11 AN: 10726

Ashkenazi Jewish (ASJ) AF: 0.00539 AC: 12 AN: 2226

East Asian (EAS) AF: 0.000202 AC: 1 AN: 4940

South Asian (SAS) AF: 0.000285 AC: 1 AN: 3512

European-Finnish (FIN) AF: 0.000594 AC: 4 AN: 6730

Middle Eastern (MID) AF: 0.0135 AC: 3 AN: 222

European-Non Finnish (NFE) AF: 0.00393 AC: 187 AN: 47524

Other (OTH) AF: 0.00214 AC: 3 AN: 1404

Alfa AF: 0.00386 Hom.: 11

ClinVar

ClinVar submissions

Significance: 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
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.3
DANN	Benign	0.89
PhyloP100		-1.9

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

Other links and lift over

dbSNP: rs184551877; hg19: chr10-47762154;