16-8858383-T-A

Position:

chr16-8858383-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014316.4(CARHSP1):c.248A>T(p.Asp83Val) variant causes a missense change. The variant allele was found at a frequency of 0.000407 in 1,613,858 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. D83A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 0 hom. )

Consequence

CARHSP1
NM_014316.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.27

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08272147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARHSP1	NM_014316.4 linkuse as main transcript	c.248A>T	p.Asp83Val	missense_variant	3/4	ENST00000311052.10
LOC100130283	NR_147908.1 linkuse as main transcript	n.635-1745T>A		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.248A>T	p.Asp83Val	missense_variant	3/4	1	NM_014316.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000467

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000482

AC:

121

AN:

251072

Hom.:

AF XY:

0.000464

AC XY:

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00158

Gnomad NFE exome

AF:

0.000722

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000401

AC:

586

AN:

1461758

Hom.:

Cov.:

AF XY:

0.000410

AC XY:

298

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00156

Gnomad4 NFE exome

AF:

0.000432

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000467

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.000646

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000579

Hom.:

Bravo

AF:

0.000253

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000379

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.000415

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

Apr 13, 2022

The c.248A>T (p.D83V) alteration is located in exon 3 (coding exon 2) of the CARHSP1 gene. This alteration results from a A to T substitution at nucleotide position 248, causing the aspartic acid (D) at amino acid position 83 to be replaced by a valine (V). 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

0.27

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

T;T;T;T;T;T;T;T;T;.;T;.;.;T

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

.;.;D;.;.;.;.;.;.;D;D;D;D;D

M_CAP

Benign

0.071

MetaRNN

Benign

0.083

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.20

MutationAssessor

Pathogenic

3.1

M;M;M;M;M;M;M;M;M;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-4.8

D;.;.;.;.;.;D;D;D;D;D;D;D;.

REVEL

Uncertain

0.30

Sift

Uncertain

0.022

D;.;.;.;.;.;D;D;D;D;D;D;D;.

Sift4G

Uncertain

0.032

D;D;D;D;D;D;D;D;D;.;.;.;.;T

Polyphen

0.95

P;P;P;P;P;P;P;P;P;.;.;.;.;.

Vest4

0.69

MVP

0.51

ClinPred

0.19

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.57

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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