chr22-40831082-C-G

Variant names:

• chr22-40831082-C-G
• rs138335
• NM_003932.5:c.682-126G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003932.5(ST13):​c.682-126G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 665,996 control chromosomes in the GnomAD database, including 157,040 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.74 (42799 hom., cov: 33)
  • Exomes 𝑓: 0.66 (114241 hom.)
• Consequence: ST13 NM_003932.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• Publications: 16 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST13	NM_003932.5	c.682-126G>C		intron_variant	Intron 8 of 11	ENST00000216218.8	NP_003923.2
ST13	NM_001278589.2	c.652-126G>C		intron_variant	Intron 8 of 11		NP_001265518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST13	ENST00000216218.8	c.682-126G>C		intron_variant	Intron 8 of 11	1	NM_003932.5	ENSP00000216218.3
ST13	ENST00000413424.5	n.*110-126G>C		intron_variant	Intron 6 of 6	3		ENSP00000412049.1
ST13	ENST00000455824.1	n.*431-126G>C		intron_variant	Intron 6 of 8	5		ENSP00000397062.1
ST13	ENST00000480048.5	n.347-126G>C		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.737 AC: 112054 AN: 152070 Hom.: 42730 Cov.: 33

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.714

GnomAD4 exome AF: 0.662 AC: 340333 AN: 513808 Hom.: 114241 AF XY: 0.661 AC XY: 179390 AN XY: 271500

African (AFR) AF: 0.938 AC: 12855 AN: 13708

American (AMR) AF: 0.819 AC: 17299 AN: 21116

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 10176 AN: 14972

East Asian (EAS) AF: 0.468 AC: 14442 AN: 30890

South Asian (SAS) AF: 0.685 AC: 30094 AN: 43922

European-Finnish (FIN) AF: 0.633 AC: 19109 AN: 30170

Middle Eastern (MID) AF: 0.731 AC: 2490 AN: 3406

European-Non Finnish (NFE) AF: 0.656 AC: 214557 AN: 327316

Other (OTH) AF: 0.682 AC: 19311 AN: 28308

GnomAD4 genome AF: 0.737 AC: 112184 AN: 152188 Hom.: 42799 Cov.: 33 AF XY: 0.736 AC XY: 54740 AN XY: 74394

African (AFR) AF: 0.938 AC: 38960 AN: 41556

American (AMR) AF: 0.782 AC: 11948 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2317 AN: 3466

East Asian (EAS) AF: 0.502 AC: 2604 AN: 5190

South Asian (SAS) AF: 0.666 AC: 3212 AN: 4826

European-Finnish (FIN) AF: 0.625 AC: 6614 AN: 10576

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44211 AN: 67982

Other (OTH) AF: 0.714 AC: 1510 AN: 2114

Alfa AF: 0.573 Hom.: 1528

Bravo AF: 0.757

Asia WGS AF: 0.595 AC: 2068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.48
DANN	Benign	0.45
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs138335; hg19: chr22-41227086; COSMIC: COSV53422406; COSMIC: COSV53422406;