NM_003922.4:c.4464-17_4464-16delTT

Variant names:

• chr15-63712910-CAA-C
• rs369792267
• NM_003922.4:c.4464-17_4464-16delTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003922.4(HERC1):​c.4464-17_4464-16delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000469 in 1,278,986 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000047 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HERC1 NM_003922.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

Genes affected

HERC1 (HGNC:4867): (HECT and RLD domain containing E3 ubiquitin protein ligase family member 1) This gen encodes a member of the HERC protein family. This protein stimulates guanine nucleotide exchange on ARF1 and Rab proteins. This protein may be involved in membrane transport processes. [provided by RefSeq, Mar 2012]

ENSG00000259589 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HERC1	NM_003922.4	c.4464-17_4464-16delTT		intron_variant	Intron 23 of 77	ENST00000443617.7	NP_003913.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HERC1	ENST00000443617.7	c.4464-17_4464-16delTT		intron_variant	Intron 23 of 77	1	NM_003922.4	ENSP00000390158.2
HERC1	ENST00000561400.1	c.1416-17_1416-16delTT		intron_variant	Intron 4 of 7	2		ENSP00000453937.1
ENSG00000259589	ENST00000559303.2	n.288-555_288-554delAA		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 143748 Hom.: 0 Cov.: 32 FAILED QC

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

GnomAD3 exomes AF: 0.0000292 AC: 4 AN: 137116 Hom.: 0 AF XY: 0.0000271 AC XY: 2 AN XY: 73780

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000303

Gnomad OTH exome AF: 0.000641

GnomAD4 exome AF: 0.00000469 AC: 6 AN: 1278986 Hom.: 0 AF XY: 0.00000315 AC XY: 2 AN XY: 634480

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000607

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 143748 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 69694

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs369792267; hg19: chr15-64005109;