1-172551580-A-G

Position:

chr1-172551580-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014283.5(SUCO):c.131A>G(p.Asp44Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000426 in 1,610,958 control chromosomes in the GnomAD database, including 2 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 2 hom. )

Consequence

SUCO
NM_014283.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:1

Conservation

PhyloP100: 2.31

Variant links:

Genes affected

SUCO (HGNC:1240): (SUN domain containing ossification factor) Predicted to be involved in positive regulation of collagen biosynthetic process; positive regulation of osteoblast differentiation; and regulation of bone remodeling. Predicted to be located in rough endoplasmic reticulum. Predicted to be active in cytoplasm and membrane. [provided by Alliance of Genome Resources, Apr 2022]

SUCO links:

SUCO (HGNC:):

SUCO links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.034301043).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUCO	NM_014283.5 linkuse as main transcript	c.131A>G	p.Asp44Gly	missense_variant	2/24	ENST00000263688.4	NP_055098.1	Q9UBS9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUCO	ENST00000263688.4 linkuse as main transcript	c.131A>G	p.Asp44Gly	missense_variant	2/24	1	NM_014283.5	ENSP00000263688.3		Q9UBS9-1

Frequencies

GnomAD3 genomes

AF:

0.000467

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

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:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000765

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000431

AC:

107

AN:

248344

Hom.:

AF XY:

0.000491

AC XY:

AN XY:

134322

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000593

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00106

Gnomad NFE exome

AF:

0.000702

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000422

AC:

616

AN:

1458856

Hom.:

Cov.:

AF XY:

0.000453

AC XY:

329

AN XY:

725704

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000676

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00137

Gnomad4 NFE exome

AF:

0.000468

Gnomad4 OTH exome

AF:

0.000299

GnomAD4 genome

AF:

0.000467

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

74300

show subpopulations

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:

0.00160

Gnomad4 NFE

AF:

0.000765

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000456

Hom.:

Bravo

AF:

0.000359

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000469

AC:

EpiCase

AF:

0.000825

EpiControl

AF:

0.000418

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:2Benign:1

Uncertain significance, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 11, 2024	This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 44 of the SUCO protein (p.Asp44Gly). This variant is present in population databases (rs145307638, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SUCO-related conditions. ClinVar contains an entry for this variant (Variation ID: 1358511). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	SUCO: BP4 -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2024

The c.131A>G (p.D44G) alteration is located in exon 2 (coding exon 2) of the SUCO gene. This alteration results from a A to G substitution at nucleotide position 131, causing the aspartic acid (D) at amino acid position 44 to be replaced by a glycine (G). 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

0.076

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0090

.;.;T;T

Eigen

Benign

0.091

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.80

.;T;T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.034

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;.;.;L

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.86

.;.;.;N

REVEL

Benign

0.081

Sift

Uncertain

0.0050

.;.;.;D

Sift4G

Benign

0.36

T;T;T;T

Polyphen

0.075, 0.72

.;.;B;P

Vest4

0.30

MVP

0.43

MPC

0.19

ClinPred

0.048

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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