1-231352778-C-T

Position:

chr1-231352778-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032018.7(SPRTN):c.887C>T(p.Pro296Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 1,613,562 control chromosomes in the GnomAD database, including 307,696 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.58 ( 25827 hom., cov: 32)

Exomes 𝑓: 0.62 ( 281869 hom. )

Consequence

SPRTN
NM_032018.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.149

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:

SPRTN (HGNC:):

SPRTN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.410465E-6).

BP6

Variant 1-231352778-C-T is Benign according to our data. Variant chr1-231352778-C-T is described in ClinVar as [Benign]. Clinvar id is 1333158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRTN	NM_032018.7 linkuse as main transcript	c.887C>T	p.Pro296Leu	missense_variant	5/5	ENST00000295050.12	NP_114407.3	Q9H040-1A0A024R3U2
SPRTN	XM_006711818.4 linkuse as main transcript	c.758C>T	p.Pro253Leu	missense_variant	4/4		XP_006711881.1
SPRTN	NM_001010984.4 linkuse as main transcript	c.*1172C>T		3_prime_UTR_variant	4/4		NP_001010984.1	Q9H040-2
SPRTN	NM_001261462.3 linkuse as main transcript	c.*1172C>T		3_prime_UTR_variant	3/3		NP_001248391.1	Q9H040-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SPRTN	ENST00000295050.12 linkuse as main transcript	c.887C>T	p.Pro296Leu	missense_variant	5/5	1	NM_032018.7	ENSP00000295050.7	Q9H040-1
SPRTN	ENST00000391858.8 linkuse as main transcript	c.*1172C>T		3_prime_UTR_variant	4/4	1		ENSP00000375731.4	Q9H040-2
SPRTN	ENST00000366644.3 linkuse as main transcript	c.*14C>T		downstream_gene_variant		5		ENSP00000355604.3	B1AKT1
SPRTN	ENST00000469904.1 linkuse as main transcript	n.*24C>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.577

AC:

87729

AN:

151960

Hom.:

25817

Cov.:

show subpopulations

Gnomad AFR

AF:

0.453

Gnomad AMI

AF:

0.638

Gnomad AMR

AF:

0.550

Gnomad ASJ

AF:

0.591

Gnomad EAS

AF:

0.553

Gnomad SAS

AF:

0.558

Gnomad FIN

AF:

0.700

Gnomad MID

AF:

0.637

Gnomad NFE

AF:

0.641

Gnomad OTH

AF:

0.593

GnomAD3 exomes

AF:

0.597

AC:

149561

AN:

250474

Hom.:

45374

AF XY:

0.601

AC XY:

81434

AN XY:

135442

show subpopulations

Gnomad AFR exome

AF:

0.451

Gnomad AMR exome

AF:

0.506

Gnomad ASJ exome

AF:

0.590

Gnomad EAS exome

AF:

0.574

Gnomad SAS exome

AF:

0.555

Gnomad FIN exome

AF:

0.689

Gnomad NFE exome

AF:

0.643

Gnomad OTH exome

AF:

0.604

GnomAD4 exome

AF:

0.619

AC:

904266

AN:

1461482

Hom.:

281869

Cov.:

AF XY:

0.618

AC XY:

449183

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.444

Gnomad4 AMR exome

AF:

0.513

Gnomad4 ASJ exome

AF:

0.586

Gnomad4 EAS exome

AF:

0.557

Gnomad4 SAS exome

AF:

0.561

Gnomad4 FIN exome

AF:

0.689

Gnomad4 NFE exome

AF:

0.633

Gnomad4 OTH exome

AF:

0.603

GnomAD4 genome

AF:

0.577

AC:

87773

AN:

152080

Hom.:

25827

Cov.:

AF XY:

0.581

AC XY:

43160

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.452

Gnomad4 AMR

AF:

0.550

Gnomad4 ASJ

AF:

0.591

Gnomad4 EAS

AF:

0.553

Gnomad4 SAS

AF:

0.559

Gnomad4 FIN

AF:

0.700

Gnomad4 NFE

AF:

0.641

Gnomad4 OTH

AF:

0.591

Alfa

AF:

0.615

Hom.:

56503

Bravo

AF:

0.561

TwinsUK

AF:

0.646

AC:

2395

ALSPAC

AF:

0.638

AC:

2458

ESP6500AA

AF:

0.468

AC:

2061

ESP6500EA

AF:

0.636

AC:

5473

ExAC

AF:

0.598

AC:

72619

Asia WGS

AF:

0.558

AC:

1939

AN:

3478

EpiCase

AF:

0.637

EpiControl

AF:

0.629

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Progeroid features-hepatocellular carcinoma predisposition syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

SPRTN-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 24, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

6.7

DANN

Benign

0.27

DEOGEN2

Benign

0.022

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0000024

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.73

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.0

REVEL

Benign

0.039

Sift

Benign

0.29

Sift4G

Benign

0.21

Polyphen

0.0

Vest4

0.014

MPC

0.019

ClinPred

0.0071

GERP RS

1.3

Varity_R

0.019

gMVP

0.60

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