dbSNP rs8097: CARHSP1:p.Arg35Arg (chr16-8859224-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP7

The NM_014316.4(CARHSP1):c.105G>T(p.Arg35Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,598,450 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 0.000021 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

CARHSP1
NM_014316.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.162

Publications

21 publications found

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:

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 Gene-Disease associations (from GenCC):

congenital disorder of glycosylation type I
Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
PMM2-congenital disorder of glycosylation
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, ClinGen

PMM2 links:

LOC100130283 (HGNC:):

LOC100130283 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP7

Synonymous conserved (PhyloP=-0.162 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARHSP1	NM_014316.4 link	c.105G>T	p.Arg35Arg	synonymous_variant	Exon 2 of 4	ENST00000311052.10	NP_055131.2	Q9Y2V2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARHSP1	ENST00000311052.10 link	c.105G>T	p.Arg35Arg	synonymous_variant	Exon 2 of 4	1	NM_014316.4	ENSP00000311847.4		Q9Y2V2

Frequencies

GnomAD3 genomes

AF:

0.0000215

AC:

AN:

139742

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000264

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000415

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

GnomAD2 exomes

AF:

0.0000736

AC:

AN:

244478

AF XY:

0.0000978

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000275

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000456

Gnomad OTH exome

AF:

0.000333

GnomAD4 exome

AF:

0.0000699

AC:

102

AN:

1458590

Hom.:

Cov.:

AF XY:

0.0000606

AC XY:

AN XY:

725604

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33454

American (AMR)

AF:

0.00

AC:

AN:

44506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39650

South Asian (SAS)

AF:

0.000105

AC:

AN:

86030

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52662

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000784

AC:

AN:

1110152

Other (OTH)

AF:

0.0000663

AC:

AN:

60296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000214

AC:

AN:

139860

Hom.:

Cov.:

AF XY:

0.0000300

AC XY:

AN XY:

66772

show subpopulations

African (AFR)

AF:

0.0000263

AC:

AN:

37972

American (AMR)

AF:

0.00

AC:

AN:

13078

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3376

East Asian (EAS)

AF:

0.000416

AC:

AN:

4802

South Asian (SAS)

AF:

0.00

AC:

AN:

3080

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65280

Other (OTH)

AF:

0.00

AC:

AN:

1722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000546

Hom.:

3172

ExAC

AF:

0.0000578

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.39

CADD

Benign

3.1

(source)

DANN

Benign

0.93

FATHMM_MKL

Uncertain

0.86

MetaRNN

Uncertain

0.47

PhyloP100

-0.16

PROVEAN

Pathogenic

-9.0

MVP

0.50

GERP RS

0.015

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over