rs369792267

Variant names:

• chr15-63712910-CAAA-C
• rs369792267
• NM_003922.4:c.4464-18_4464-16delTTT

Your query was ambiguous. Multiple possible variants found:

• chr15-63712910-CAAA-C
• chr15-63712910-CAAA-CA
• chr15-63712910-CAAA-CAA
• chr15-63712910-CAAA-CAAAA
• chr15-63712910-CAAA-CAAAAA
• chr15-63712910-CAAA-CAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003922.4(HERC1):​c.4464-18_4464-16delTTT variant causes a intron change. The variant allele was found at a frequency of 0.00000696 in 143,748 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 0.0000070 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HERC1 NM_003922.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.05
• Publications: 0 publications found

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]

HERC1 Gene-Disease associations (from GenCC):

• macrocephaly, dysmorphic facies, and psychomotor retardation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• megalencephaly-severe kyphoscoliosis-overgrowth syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000259589 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 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.4464-18_4464-16delTTT		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.4464-18_4464-16delTTT		intron_variant	Intron 23 of 77	1	NM_003922.4	ENSP00000390158.2
HERC1	ENST00000561400.1	c.1416-18_1416-16delTTT		intron_variant	Intron 4 of 7	2		ENSP00000453937.1
ENSG00000259589	ENST00000559303.2	n.288-555_288-553delAAA		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.00000696 AC: 1 AN: 143748 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000255

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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1279330 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 634642

African (AFR) AF: 0.00 AC: 0 AN: 28562

American (AMR) AF: 0.00 AC: 0 AN: 33058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21848

East Asian (EAS) AF: 0.00 AC: 0 AN: 34062

South Asian (SAS) AF: 0.00 AC: 0 AN: 70700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5048

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 988306

Other (OTH) AF: 0.00 AC: 0 AN: 52136

GnomAD4 genome AF: 0.00000696 AC: 1 AN: 143748 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 69694

African (AFR) AF: 0.0000255 AC: 1 AN: 39176

American (AMR) AF: 0.00 AC: 0 AN: 14542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3354

East Asian (EAS) AF: 0.00 AC: 0 AN: 4972

South Asian (SAS) AF: 0.00 AC: 0 AN: 4542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8908

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65098

Other (OTH) AF: 0.00 AC: 0 AN: 1976

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs369792267; hg19: chr15-64005109;