Variant 16-8859243-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014316.4(CARHSP1):c.86G>A(p.Arg29His) variant causes a missense change. The variant allele was found at a frequency of 0.00007 in 1,600,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R29P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

CARHSP1
NM_014316.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.61

Variant links:

Genes affected

CARHSP1 (HGNC:17150): (calcium regulated heat stable protein 1) Enables mRNA 3'-UTR binding activity. Predicted to be involved in regulation of mRNA stability. Predicted to be located in P granule and cytosol. Predicted to be active in cytoplasm. Predicted to colocalize with cytoplasmic exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

CARHSP1 links:

LOC100130283 (HGNC:):

LOC100130283 links:

PMM2 (HGNC:9115): (phosphomannomutase 2) The protein encoded by this gene catalyzes the isomerization of mannose 6-phosphate to mannose 1-phosphate, which is a precursor to GDP-mannose necessary for the synthesis of dolichol-P-oligosaccharides. Mutations in this gene have been shown to cause defects in glycoprotein biosynthesis, which manifests as carbohydrate-deficient glycoprotein syndrome type I. [provided by RefSeq, Jul 2008]

PMM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2992883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARHSP1	NM_014316.4 linkuse as main transcript	c.86G>A	p.Arg29His	missense_variant	2/4	ENST00000311052.10
LOC100130283	NR_147908.1 linkuse as main transcript	n.635-885C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARHSP1	ENST00000311052.10 linkuse as main transcript	c.86G>A	p.Arg29His	missense_variant	2/4	1	NM_014316.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000128

AC:

AN:

140768

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000761

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000326

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000122

Gnomad OTH

AF:

0.000574

GnomAD3 exomes

AF:

0.0000611

AC:

AN:

245698

Hom.:

AF XY:

0.0000299

AC XY:

AN XY:

133698

show subpopulations

Gnomad AFR exome

AF:

0.0000633

Gnomad AMR exome

AF:

0.0000583

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.0000478

Gnomad NFE exome

AF:

0.0000454

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000644

AC:

AN:

1459822

Hom.:

Cov.:

AF XY:

0.0000606

AC XY:

AN XY:

726262

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000684

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000128

AC:

AN:

140768

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

67304

show subpopulations

Gnomad4 AFR

AF:

0.000183

Gnomad4 AMR

AF:

0.0000761

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000326

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000122

Gnomad4 OTH

AF:

0.000574

Alfa

AF:

0.0000773

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2023

The c.86G>A (p.R29H) alteration is located in exon 2 (coding exon 1) of the CARHSP1 gene. This alteration results from a G to A substitution at nucleotide position 86, causing the arginine (R) at amino acid position 29 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Uncertain

-0.030

Cadd

Benign

Dann

Benign

0.95

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

1.0

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.30

MutationTaster

Benign

1.0

D;D;D;D;D

PROVEAN

Uncertain

-4.0

MVP

0.16

ClinPred

0.18

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over