3-57677221-C-T

Variant names:

• chr3-57677221-C-T
• rs17058450
• NM_152678.3:c.238-4783G>A

Variant summary

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

The NM_152678.3(DENND6A):​c.238-4783G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,110 control chromosomes in the GnomAD database, including 1,350 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 0.13 (1350 hom., cov: 32)
• Consequence: DENND6A NM_152678.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893
• Publications: 3 publications found

Genes affected

DENND6A (HGNC:26635): (DENN domain containing 6A) Enables guanyl-nucleotide exchange factor activity. Involved in positive regulation of cell-cell adhesion mediated by cadherin. Located in recycling endosome. [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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENND6A	NM_152678.3	c.238-4783G>A		intron_variant	Intron 1 of 19	ENST00000311128.10	NP_689891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DENND6A	ENST00000311128.10	c.238-4783G>A		intron_variant	Intron 1 of 19	1	NM_152678.3	ENSP00000311401.5
DENND6A	ENST00000464875.1	n.64-4783G>A		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19418 AN: 151992 Hom.: 1349 Cov.: 32

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.0912

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0772

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.121

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.128 AC: 19411 AN: 152110 Hom.: 1350 Cov.: 32 AF XY: 0.126 AC XY: 9395 AN XY: 74360

African (AFR) AF: 0.0886 AC: 3678 AN: 41498

American (AMR) AF: 0.0915 AC: 1399 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3468

East Asian (EAS) AF: 0.0770 AC: 399 AN: 5182

South Asian (SAS) AF: 0.211 AC: 1017 AN: 4816

European-Finnish (FIN) AF: 0.118 AC: 1245 AN: 10564

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10702 AN: 67982

Other (OTH) AF: 0.120 AC: 253 AN: 2108

Alfa AF: 0.0944 Hom.: 185

Bravo AF: 0.121

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.44
DANN	Benign	0.35
PhyloP100		-0.89
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: rs17058450; hg19: chr3-57662948;