1-172551570-T-C

Variant names:

• chr1-172551570-T-C
• NM_014283.5:c.121T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014283.5(SUCO):​c.121T>C​(p.Tyr41His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SUCO NM_014283.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUCO	NM_014283.5	c.121T>C	p.Tyr41His	missense_variant	Exon 2 of 24	ENST00000263688.4	NP_055098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCO	ENST00000263688.4	c.121T>C	p.Tyr41His	missense_variant	Exon 2 of 24	1	NM_014283.5	ENSP00000263688.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.121T>C (p.Y41H) alteration is located in exon 2 (coding exon 2) of the SUCO gene. This alteration results from a T to C substitution at nucleotide position 121, causing the tyrosine (Y) at amino acid position 41 to be replaced by a histidine (H). 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	0.13
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	.;.;T;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.80	.;T;T;T
M_CAP	Benign	0.0057	T
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	2.0	.;.;.;M
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.62	N;.;.;N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D;.;.;D
Sift4G	Benign	0.25	T;T;T;T
Polyphen		1.0, 1.0	.;.;D;D
Vest4		0.71
MVP		0.48
MPC		0.47
ClinPred		0.83	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-172520710;