13-39013046-T-C

Position:

• chr13-39013046-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_025138.5(PROSER1):​c.2206A>G​(p.Thr736Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: PROSER1 NM_025138.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04411784).
• BP6: Variant 13-39013046-T-C is Benign according to our data. Variant chr13-39013046-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3310317.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROSER1	NM_025138.5	c.2206A>G	p.Thr736Ala	missense_variant	11/13	ENST00000352251.8
PROSER1	NM_170719.4	c.2140A>G	p.Thr714Ala	missense_variant	10/12
PROSER1	XM_011535239.4	c.2119A>G	p.Thr707Ala	missense_variant	10/12
PROSER1	XM_047430652.1	c.2053A>G	p.Thr685Ala	missense_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROSER1	ENST00000352251.8	c.2206A>G	p.Thr736Ala	missense_variant	11/13	1	NM_025138.5	P1
PROSER1	ENST00000625998.2	c.2140A>G	p.Thr714Ala	missense_variant	10/12	5
PROSER1	ENST00000484434.3	n.709-857A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151860 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151860 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74152

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.019
DANN	Benign	0.72
DEOGEN2	Benign	0.0063	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.044	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.14	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.16	N;.
REVEL	Benign	0.016
Sift	Benign	0.45	T;.
Sift4G	Benign	0.21	T;T
Polyphen		0.0	B;.
Vest4		0.042
MutPred		0.27		Loss of glycosylation at T736 (P = 0.0018);.;
MVP		0.068
MPC		0.067
ClinPred		0.028	T
GERP RS		-5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.014
gMVP		0.12

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: rs1482848617; hg19: chr13-39587183;