rs6927608

Variant names:

• chr6-104840250-A-C
• rs6927608
• NM_020771.4:c.402+2973T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-104840250-A-C
• chr6-104840250-A-T

Variant summary

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

The NM_020771.4(HACE1):​c.402+2973T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,248 control chromosomes in the GnomAD database, including 972 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 0.11 (972 hom., cov: 32)
• Consequence: HACE1 NM_020771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.307
• Publications: 8 publications found

Genes affected

HACE1 (HGNC:21033): (HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1) This gene encodes a HECT domain and ankyrin repeat-containing ubiquitin ligase. The encoded protein is involved in specific tagging of target proteins, leading to their subcellular localization or proteasomal degradation. The protein is a potential tumor suppressor and is involved in the pathophysiology of several tumors, including Wilm's tumor. [provided by RefSeq, Mar 2016]

HACE1 Gene-Disease associations (from GenCC):

• spastic paraplegia-severe developmental delay-epilepsy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000227535 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020771.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HACE1	NM_020771.4	MANE Select	c.402+2973T>G		intron	N/A	NP_065822.2	Q8IYU2-1
	HACE1	NM_001321083.2		c.300+2973T>G		intron	N/A	NP_001308012.1
	HACE1	NM_001321080.2		c.402+2973T>G		intron	N/A	NP_001308009.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HACE1	ENST00000262903.9	TSL:1 MANE Select	c.402+2973T>G		intron	N/A	ENSP00000262903.4	Q8IYU2-1
	HACE1	ENST00000416605.6	TSL:1	n.402+2973T>G		intron	N/A	ENSP00000392425.2	E3W983
	HACE1	ENST00000851410.1		c.402+2973T>G		intron	N/A	ENSP00000521469.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16825 AN: 152130 Hom.: 972 Cov.: 32

Gnomad AFR AF: 0.0734

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.110 AC: 16814 AN: 152248 Hom.: 972 Cov.: 32 AF XY: 0.116 AC XY: 8606 AN XY: 74424

African (AFR) AF: 0.0731 AC: 3040 AN: 41560

American (AMR) AF: 0.154 AC: 2356 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0995 AC: 345 AN: 3466

East Asian (EAS) AF: 0.154 AC: 796 AN: 5182

South Asian (SAS) AF: 0.150 AC: 720 AN: 4816

European-Finnish (FIN) AF: 0.167 AC: 1762 AN: 10582

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7498 AN: 68024

Other (OTH) AF: 0.104 AC: 219 AN: 2112

Alfa AF: 0.112 Hom.: 1428

Bravo AF: 0.109

Asia WGS AF: 0.140 AC: 488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.8
DANN	Benign	0.77
PhyloP100		0.31
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: rs6927608; hg19: chr6-105288125; COSMIC: COSV53507308; COSMIC: COSV53507308;