chr13-39012115-T-G

Position:

• chr13-39012115-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_025138.5(PROSER1):​c.2680A>C​(p.Asn894His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PROSER1 NM_025138.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.63

Genes affected

PROSER1 (HGNC:20291): (proline and serine rich 1) This gene encodes a conserved protein containing proline and serine rich regions. These regions may be important in protein-protein interactions. [provided by RefSeq, Aug 2012]

ACMG classification

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=0.2669254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROSER1	NM_025138.5	c.2680A>C	p.Asn894His	missense_variant	12/13	ENST00000352251.8
PROSER1	NM_170719.4	c.2614A>C	p.Asn872His	missense_variant	11/12
PROSER1	XM_011535239.4	c.2593A>C	p.Asn865His	missense_variant	11/12
PROSER1	XM_047430652.1	c.2527A>C	p.Asn843His	missense_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROSER1	ENST00000352251.8	c.2680A>C	p.Asn894His	missense_variant	12/13	1	NM_025138.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461844 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727218

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.2680A>C (p.N894H) alteration is located in exon 12 (coding exon 12) of the PROSER1 gene. This alteration results from a A to C substitution at nucleotide position 2680, causing the asparagine (N) at amino acid position 894 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	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.34	N;.
MutationTaster	Benign	0.53	N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.0	N;.
REVEL	Benign	0.17
Sift	Uncertain	0.013	D;.
Sift4G	Uncertain	0.012	D;D
Polyphen		0.99	D;.
Vest4		0.34
MutPred		0.28		Gain of glycosylation at S899 (P = 0.2306);.;
MVP		0.068
MPC		0.37
ClinPred		0.61	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-39586252;