12-110016585-C-T

Variant names:

• chr12-110016585-C-T
• rs7295290
• NM_033121.2:c.400+152C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033121.2(ANKRD13A):​c.400+152C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0739 in 670,132 control chromosomes in the GnomAD database, including 2,276 homozygotes. 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: 𝑓 0.082 (550 hom., cov: 32)
  • Exomes 𝑓: 0.071 (1726 hom.)
• Consequence: ANKRD13A NM_033121.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176
• Publications: 5 publications found

Genes affected

ANKRD13A (HGNC:21268): (ankyrin repeat domain 13A) Enables ubiquitin-dependent protein binding activity. Involved in negative regulation of protein localization to endosome and negative regulation of receptor internalization. Located in late endosome; perinuclear region of cytoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0922 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033121.2. 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
	ANKRD13A	NM_033121.2	MANE Select	c.400+152C>T		intron	N/A	NP_149112.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD13A	ENST00000261739.9	TSL:1 MANE Select	c.400+152C>T		intron	N/A	ENSP00000261739.4
	ANKRD13A	ENST00000550404.1	TSL:1	n.659+152C>T		intron	N/A
	ANKRD13A	ENST00000553025.5	TSL:1	n.136+152C>T		intron	N/A	ENSP00000474172.1

Frequencies

GnomAD3 genomes AF: 0.0822 AC: 12490 AN: 151970 Hom.: 549 Cov.: 32

Gnomad AFR AF: 0.0946

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0703

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0831

Gnomad FIN AF: 0.0713

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.100

GnomAD4 exome AF: 0.0715 AC: 37018 AN: 518044 Hom.: 1726 AF XY: 0.0723 AC XY: 19122 AN XY: 264360

African (AFR) AF: 0.0936 AC: 1301 AN: 13896

American (AMR) AF: 0.0558 AC: 936 AN: 16782

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 1741 AN: 12200

East Asian (EAS) AF: 0.000232 AC: 7 AN: 30134

South Asian (SAS) AF: 0.0717 AC: 2252 AN: 31402

European-Finnish (FIN) AF: 0.0593 AC: 1685 AN: 28404

Middle Eastern (MID) AF: 0.120 AC: 228 AN: 1904

European-Non Finnish (NFE) AF: 0.0751 AC: 26825 AN: 357390

Other (OTH) AF: 0.0788 AC: 2043 AN: 25932

GnomAD4 genome AF: 0.0822 AC: 12500 AN: 152088 Hom.: 550 Cov.: 32 AF XY: 0.0814 AC XY: 6053 AN XY: 74322

African (AFR) AF: 0.0946 AC: 3925 AN: 41480

American (AMR) AF: 0.0702 AC: 1074 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 498 AN: 3470

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5168

South Asian (SAS) AF: 0.0830 AC: 400 AN: 4820

European-Finnish (FIN) AF: 0.0713 AC: 752 AN: 10540

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0819 AC: 5568 AN: 68002

Other (OTH) AF: 0.0999 AC: 211 AN: 2112

Alfa AF: 0.0843 Hom.: 109

Bravo AF: 0.0828

Asia WGS AF: 0.0390 AC: 137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.76
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs7295290; hg19: chr12-110454390;