rs41290563

Variant names:

• chr5-151103696-G-A
• rs41290563
• NM_001155.5:c.1840-4C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-151103696-G-A
• chr5-151103696-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001155.5(ANXA6):​c.1840-4C>T variant causes a splice region, intron 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANXA6 NM_001155.5 splice_region, intron
• Scores: Splicing: ADA: 0.0007237
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.919

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA6	NM_001155.5	c.1840-4C>T		splice_region_variant, intron_variant	Intron 24 of 25	ENST00000354546.10	NP_001146.2
ANXA6	NM_001363114.2	c.1822-4C>T		splice_region_variant, intron_variant	Intron 23 of 24		NP_001350043.1
ANXA6	NM_001193544.2	c.1744-4C>T		splice_region_variant, intron_variant	Intron 23 of 24		NP_001180473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA6	ENST00000354546.10	c.1840-4C>T		splice_region_variant, intron_variant	Intron 24 of 25	1	NM_001155.5	ENSP00000346550.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000420 AC: 1 AN: 237926 Hom.: 0 AF XY: 0.00000776 AC XY: 1 AN XY: 128912

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000925

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00072
dbscSNV1_RF	Benign	0.014
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs41290563; hg19: chr5-150483257;