Variant rs527236213 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_032018.7(SPRTN):c.350A>G(p.Tyr117Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,461,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SPRTN
NM_032018.7 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.61

Variant links:

Genes affected

SPRTN (HGNC:25356): (SprT-like N-terminal domain) The protein encoded by this gene may play a role in DNA repair during replication of damaged DNA. This protein recruits valosin containing protein (p97) to stalled DNA replication forks where it may prevent excessive translesional DNA synthesis and limit the number of DNA-damage induced mutations. It may also be involved in replication-related G2/M-checkpoint regulation. Deficiency of a similar protein in mouse causes chromosomal instability and progeroid phenotypes. Mutations in this gene have been associated with Ruijs-Aalfs syndrome (RJALS). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2015]

SPRTN links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.845

PP5

Variant 1-231347825-A-G is Pathogenic according to our data. Variant chr1-231347825-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 143916.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-231347825-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPRTN	NM_032018.7 linkuse as main transcript	c.350A>G	p.Tyr117Cys	missense_variant	3/5	ENST00000295050.12
SPRTN	NM_001010984.4 linkuse as main transcript	c.350A>G	p.Tyr117Cys	missense_variant	3/4
SPRTN	NM_001261462.3 linkuse as main transcript	c.322-3479A>G		intron_variant
SPRTN	XM_006711818.4 linkuse as main transcript	c.322-3479A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPRTN	ENST00000295050.12 linkuse as main transcript	c.350A>G	p.Tyr117Cys	missense_variant	3/5	1	NM_032018.7	P1	Q9H040-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250622

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135472

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461164

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726896

show subpopulations

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:

0.0000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Progeroid features-hepatocellular carcinoma predisposition syndrome

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

.;T;T

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.84

D;D;D

MetaSVM

Benign

-0.53

MutationAssessor

Pathogenic

3.3

M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-4.7

D;D;D

REVEL

Pathogenic

0.77

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.030

D;D;D

Polyphen

0.65

P;P;.

Vest4

0.86

MutPred

0.61

Gain of catalytic residue at L118 (P = 0.0168);Gain of catalytic residue at L118 (P = 0.0168);.;

MVP

0.80

MPC

2.1

ClinPred

0.95

GERP RS

5.7

Varity_R

0.82

gMVP

0.85

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

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