19-32643729-A-T

Variant names:

• chr19-32643729-A-T
• rs259228
• NM_032139.3:c.526-98T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032139.3(ANKRD27):​c.526-98T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 30)
  • Exomes 𝑓: 9.6e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD27 NM_032139.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.784
• Publications: 0 publications found

Genes affected

ANKRD27 (HGNC:25310): (ankyrin repeat domain 27) Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in endocytic recycling and negative regulation of SNARE complex assembly. Acts upstream of or within early endosome to late endosome transport. Located in endosome; lysosome; and plasma membrane. Implicated in eosinophilic esophagitis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032139.3. 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
	ANKRD27	NM_032139.3	MANE Select	c.526-98T>A		intron	N/A	NP_115515.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD27	ENST00000306065.9	TSL:1 MANE Select	c.526-98T>A		intron	N/A	ENSP00000304292.3
	ANKRD27	ENST00000587352.5	TSL:1	c.526-98T>A		intron	N/A	ENSP00000466138.1
	ANKRD27	ENST00000593232.5	TSL:2	n.57T>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151828 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.60e-7 AC: 1 AN: 1041592 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 532194

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24994

American (AMR) AF: 0.00 AC: 0 AN: 42032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22938

East Asian (EAS) AF: 0.00 AC: 0 AN: 37484

South Asian (SAS) AF: 0.00 AC: 0 AN: 76232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3598

European-Non Finnish (NFE) AF: 0.00000135 AC: 1 AN: 739546

Other (OTH) AF: 0.00 AC: 0 AN: 46316

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151828 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74090

African (AFR) AF: 0.00 AC: 0 AN: 41328

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2084

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.91
DANN	Benign	0.51
PhyloP100		-0.78
PromoterAI		-0.0044	Neutral

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: rs259228; hg19: chr19-33134635;