10-60685064-T-G

Variant names:

• chr10-60685064-T-G
• rs1837949
• ENST00000373827.6:c.57+48199A>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The ENST00000373827.6(ANK3):​c.57+48199A>C variant causes a intron change. The variant allele was found at a frequency of 0.0000135 in 1,186,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: ANK3 ENST00000373827.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00
• Publications: 5 publications found

Genes affected

ANK3 (HGNC:494): (ankyrin 3) Ankyrins are a family of proteins that are believed to link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact, and the maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. Ankyrin 3 is an immunologically distinct gene product from ankyrins 1 and 2, and was originally found at the axonal initial segment and nodes of Ranvier of neurons in the central and peripheral nervous systems. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

ARL4AP1 (HGNC:17741): (ADP ribosylation factor like GTPase 4A pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BS1: Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0000135 (16/1186376) while in subpopulation SAS AF = 0.000192 (15/78054). AF 95% confidence interval is 0.000118. There are 0 homozygotes in GnomAdExome4. There are 8 alleles in the male GnomAdExome4 subpopulation. Median coverage is 16. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000373827.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	NM_001204403.2		c.57+48199A>C		intron	N/A	NP_001191332.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	ENST00000373827.6	TSL:1	c.57+48199A>C		intron	N/A	ENSP00000362933.2
	ARL4AP1	ENST00000503220.1	TSL:6	n.560T>G		non_coding_transcript_exon	Exon 1 of 1
	ANK3	ENST00000510382.1	TSL:2	n.62+48199A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000135 AC: 16 AN: 1186376 Hom.: 0 Cov.: 16 AF XY: 0.0000134 AC XY: 8 AN XY: 599198

African (AFR) AF: 0.00 AC: 0 AN: 27048

American (AMR) AF: 0.00 AC: 0 AN: 37716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21622

East Asian (EAS) AF: 0.00 AC: 0 AN: 31884

South Asian (SAS) AF: 0.000192 AC: 15 AN: 78054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46674

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4948

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 889518

Other (OTH) AF: 0.0000204 AC: 1 AN: 48912

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.58
PhyloP100		4.0

Splicing

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

Other links and lift over

dbSNP: rs1837949; hg19: chr10-62444822;