1-186189762-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_031935.3(HMCN1):​c.16792C>T​(p.Arg5598*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000821 in 1,461,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Synonymous variant affecting the same amino acid position (i.e. R5598R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

HMCN1
NM_031935.3 stop_gained

Scores

5
1
1

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 4.96
Variant links:
Genes affected
HMCN1 (HGNC:19194): (hemicentin 1) This gene encodes a large extracellular member of the immunoglobulin superfamily. A similar protein in C. elegans forms long, fine tracks at specific extracellular sites that are involved in many processes such as stabilization of the germline syncytium, anchorage of mechanosensory neurons to the epidermis, and organization of hemidesmosomes in the epidermis. Mutations in this gene may be associated with age-related macular degeneration. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HMCN1NM_031935.3 linkc.16792C>T p.Arg5598* stop_gained Exon 107 of 107 ENST00000271588.9 NP_114141.2 Q96RW7-1
HMCN1XM_011510038.4 linkc.16441C>T p.Arg5481* stop_gained Exon 106 of 106 XP_011508340.1 Q96RW7-2
HMCN1XM_017002437.2 linkc.14815C>T p.Arg4939* stop_gained Exon 96 of 96 XP_016857926.1
HMCN1XM_047431608.1 linkc.12616C>T p.Arg4206* stop_gained Exon 84 of 84 XP_047287564.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HMCN1ENST00000271588.9 linkc.16792C>T p.Arg5598* stop_gained Exon 107 of 107 1 NM_031935.3 ENSP00000271588.4 Q96RW7-1
HMCN1ENST00000414277.1 linkc.*97C>T downstream_gene_variant 3 ENSP00000406205.1 Q5TCP6

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
152124
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:
0.00000399
AC:
1
AN:
250408
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135314
show subpopulations
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:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461432
Hom.:
0
Cov.:
32
AF XY:
0.0000110
AC XY:
8
AN XY:
727010
show subpopulations
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:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
152242
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74440
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
Alfa
AF:
0.0000283
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Prostate cancer Uncertain:1
-
Science for Life laboratory, Karolinska Institutet
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.62
D
BayesDel_noAF
Pathogenic
0.66
CADD
Pathogenic
45
DANN
Uncertain
0.99
Eigen
Pathogenic
0.83
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
0.99
D
Vest4
0.68
GERP RS
5.9

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs193921043; hg19: chr1-186158894; COSMIC: COSV54900490; COSMIC: COSV54900490; API