5-32588543-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006713.4(SUB1):c.31A>T(p.Ser11Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S11G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SUB1 NM_006713.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.08

Genes affected

SUB1 (HGNC:19985): (SUB1 regulator of transcription) Enables identical protein binding activity; single-stranded DNA binding activity; and transcription coactivator activity. Involved in negative regulation of DNA metabolic process and regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. Part of transcription regulator complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.377948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUB1	NM_006713.4	c.31A>T	p.Ser11Cys	missense_variant	2/5	ENST00000265073.9
SUB1	XM_011513944.4	c.31A>T	p.Ser11Cys	missense_variant	3/6
SUB1	XM_047416661.1	c.31A>T	p.Ser11Cys	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUB1	ENST00000265073.9	c.31A>T	p.Ser11Cys	missense_variant	2/5	1	NM_006713.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
Cadd	Uncertain	26
Dann	Uncertain	0.98
DEOGEN2	Benign	0.093	T;T;T;T;T;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.38	T;T;T;T;T;T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	1.9	L;L;L;L;L;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-2.0	N;N;N;N;N;D
REVEL	Benign	0.17
Sift	Uncertain	0.0080	D;D;D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D;D;D
Polyphen		1.0	D;D;D;D;D;.
Vest4		0.42
MutPred		0.32		Loss of phosphorylation at S11 (P = 5e-04);Loss of phosphorylation at S11 (P = 5e-04);Loss of phosphorylation at S11 (P = 5e-04);Loss of phosphorylation at S11 (P = 5e-04);Loss of phosphorylation at S11 (P = 5e-04);Loss of phosphorylation at S11 (P = 5e-04);
MVP		0.51
MPC		0.071
ClinPred		0.79	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs17850527; hg19: chr5-32588649;