16-8859179-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4 BP6_Moderate BP7

The NM_014316.4(CARHSP1):c.150C>G(p.Thr50=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000214 in 1,451,472 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: CARHSP1 NM_014316.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0850

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]

LOC100130283 (HGNC:):

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.351184).
• BP6: Variant 16-8859179-G-C is Benign according to our data. Variant chr16-8859179-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2646183.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.085 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARHSP1	NM_014316.4	c.150C>G	p.Thr50=	synonymous_variant	2/4	ENST00000311052.10
LOC100130283	NR_147908.1	n.635-949G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARHSP1	ENST00000311052.10	c.150C>G	p.Thr50=	synonymous_variant	2/4	1	NM_014316.4	P1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD3 exomes AF: 0.0000453 AC: 11 AN: 242740 Hom.: 0 AF XY: 0.0000606 AC XY: 8 AN XY: 132072

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: 0.000200

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000461

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000214 AC: 31 AN: 1451472 Hom.: 0 Cov.: 29 AF XY: 0.0000305 AC XY: 22 AN XY: 720978

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: 0.000234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000815

Gnomad4 OTH exome AF: 0.0000334

GnomAD4 genome Cov.: 29

Alfa AF: 0.0000712 Hom.: 0

ExAC AF: 0.0000577 AC: 7

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

CARHSP1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	6.8
Dann	Benign	0.89
FATHMM_MKL	Pathogenic	0.97	D
MetaRNN	Benign	0.35	T
MutationTaster	Benign	1.0	D;D;D;D;D
PROVEAN	Pathogenic	-9.0	D
MVP		0.43
GERP RS		1.1
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

LitVar

Other links and lift over

dbSNP: rs758440108; hg19: chr16-8953036;