Variant 19-19297106-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_172231.4(SUGP1):c.1126G>A(p.Ala376Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,613,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

SUGP1
NM_172231.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.01

Variant links:

Genes affected

SUGP1 (HGNC:18643): (SURP and G-patch domain containing 1) SF4 is a member of the SURP family of splicing factors.[supplied by OMIM, Sep 2003]

SUGP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005758971).

BP6

Variant 19-19297106-C-T is Benign according to our data. Variant chr19-19297106-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3323563.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 100 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUGP1	NM_172231.4 linkuse as main transcript	c.1126G>A	p.Ala376Thr	missense_variant	8/14	ENST00000247001.10	NP_757386.2
SUGP1	XM_047439142.1 linkuse as main transcript	c.496G>A	p.Ala166Thr	missense_variant	6/12		XP_047295098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUGP1	ENST00000247001.10 linkuse as main transcript	c.1126G>A	p.Ala376Thr	missense_variant	8/14	1	NM_172231.4	ENSP00000247001	P1	Q8IWZ8-1

Frequencies

GnomAD3 genomes

AF:

0.000657

AC:

100

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000160

AC:

AN:

250446

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135488

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000677

AC:

AN:

1461590

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.00158

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000657

AC:

100

AN:

152264

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000118

Hom.:

Bravo

AF:

0.000559

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000123

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 21, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.7

DANN

Benign

0.57

DEOGEN2

Benign

0.018

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.54

M_CAP

Benign

0.0061

MetaRNN

Benign

0.0058

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.020

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.50

REVEL

Benign

0.062

Sift

Benign

0.68

Sift4G

Benign

0.58

Polyphen

0.0010

Vest4

0.053

MVP

0.10

MPC

0.20

ClinPred

0.0023

GERP RS

0.89

Varity_R

0.031

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