rs17850527

Positions:

• chr5-32588543-A-G
• chr5-32588543-A-T

Variant summary

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

The ENST00000265073.9(SUB1):​c.31A>G​(p.Ser11Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,880 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SUB1 ENST00000265073.9 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=0.33599216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUB1	NM_006713.4	c.31A>G	p.Ser11Gly	missense_variant	2/5	ENST00000265073.9	NP_006704.3
SUB1	XM_011513944.4	c.31A>G	p.Ser11Gly	missense_variant	3/6		XP_011512246.1
SUB1	XM_047416661.1	c.31A>G	p.Ser11Gly	missense_variant	3/6		XP_047272617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUB1	ENST00000265073.9	c.31A>G	p.Ser11Gly	missense_variant	2/5	1	NM_006713.4	ENSP00000265073	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460880 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726760

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.095	T;T;T;T;T;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	.;.;.;.;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.34	T;T;T;T;T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.9	L;L;L;L;L;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.1	N;N;N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.057	T;T;T;T;T;D
Sift4G	Uncertain	0.033	D;D;D;D;D;D
Polyphen		0.92	P;P;P;P;P;.
Vest4		0.36
MutPred		0.099		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		0.55
MPC		0.068
ClinPred		0.77	D
GERP RS		5.7
Varity_R		0.17
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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;