rs1299307424

Variant names:

• chr22-40827097-T-A
• rs1299307424
• NM_003932.5:c.980A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003932.5(ST13):​c.980A>T​(p.Gln327Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000685 in 1,459,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q327H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ST13 NM_003932.5 missense, splice_region
• Scores: Splicing: ADA: 0.5887
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.80
• Publications: 0 publications found

Genes affected

ST13 (HGNC:11343): (ST13 Hsp70 interacting protein) The protein encoded by this gene is an adaptor protein that mediates the association of the heat shock proteins HSP70 and HSP90. This protein has been shown to be involved in the assembly process of glucocorticoid receptor, which requires the assistance of multiple molecular chaperones. The expression of this gene is reported to be downregulated in colorectal carcinoma tissue suggesting that it is a candidate tumor suppressor gene. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3689954).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003932.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST13	NM_003932.5	MANE Select	c.980A>T	p.Gln327Leu	missense splice_region	Exon 11 of 12	NP_003923.2
	ST13	NM_001278589.2		c.950A>T	p.Gln317Leu	missense splice_region	Exon 11 of 12	NP_001265518.1	B4E0U6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST13	ENST00000216218.8	TSL:1 MANE Select	c.980A>T	p.Gln327Leu	missense splice_region	Exon 11 of 12	ENSP00000216218.3	P50502
	ST13	ENST00000893870.1		c.1097A>T	p.Gln366Leu	missense splice_region	Exon 12 of 13	ENSP00000563929.1
	ST13	ENST00000893867.1		c.1055A>T	p.Gln352Leu	missense splice_region	Exon 12 of 13	ENSP00000563926.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 250682 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459320 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725968

African (AFR) AF: 0.00 AC: 0 AN: 33408

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4156

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111660

Other (OTH) AF: 0.00 AC: 0 AN: 60194

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Benign	0.067
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.96	T
PhyloP100		4.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.21
Sift	Benign	0.035	D
Sift4G	Uncertain	0.028	D
Polyphen		0.043	B
Vest4		0.58
MutPred		0.28		Loss of disorder (P = 0.0411)
MVP		0.61
MPC		0.52
ClinPred		0.97	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.65
Mutation Taster		=34/66	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.59
dbscSNV1_RF	Benign	0.46
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

Other links and lift over

dbSNP: rs1299307424; hg19: chr22-41223101;