rs778131898

Variant names:

• chr11-2302174-G-T
• rs778131898
• NM_139022.3:c.25G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_139022.3(TSPAN32):​c.25G>T​(p.Val9Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000158 in 1,268,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: TSPAN32 NM_139022.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.538
• Publications: 0 publications found

Genes affected

TSPAN32 (HGNC:13410): (tetraspanin 32) This gene, which is a member of the tetraspanin superfamily, is one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of chromosome 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian and breast cancers. This gene is located among several imprinted genes; however, this gene, as well as the tumor-suppressing subchromosomal transferable fragment 4, escapes imprinting. This gene may play a role in malignancies and diseases that involve this region, and it is also involved in hematopoietic cell function. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

C11orf21 (HGNC:13231): (chromosome 11 open reading frame 21) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139022.3. 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
	TSPAN32	NM_139022.3	MANE Select	c.25G>T	p.Val9Phe	missense	Exon 1 of 10	NP_620591.3	Q96QS1-1
	C11orf21	NR_138249.2		n.259+708C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN32	ENST00000182290.9	TSL:1 MANE Select	c.25G>T	p.Val9Phe	missense	Exon 1 of 10	ENSP00000182290.5	Q96QS1-1
	TSPAN32	ENST00000446063.6	TSL:1	n.25G>T		non_coding_transcript_exon	Exon 1 of 10	ENSP00000395018.2	Q96QS1-5
	TSPAN32	ENST00000483227.5	TSL:1	n.28G>T		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000160 AC: 2 AN: 125306 AF XY: 0.0000300

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000968

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000158 AC: 2 AN: 1268074 Hom.: 0 Cov.: 39 AF XY: 0.00000325 AC XY: 2 AN XY: 614490

African (AFR) AF: 0.00 AC: 0 AN: 27620

American (AMR) AF: 0.00 AC: 0 AN: 20220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17710

East Asian (EAS) AF: 0.0000291 AC: 1 AN: 34416

South Asian (SAS) AF: 0.0000195 AC: 1 AN: 51346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4976

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1014530

Other (OTH) AF: 0.00 AC: 0 AN: 51670

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000881 AC: 1

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	Benign	0.16
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.54
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.062
Sift	Benign	0.033	D
Sift4G	Uncertain	0.037	D
Polyphen		0.026	B
Vest4		0.37
MutPred		0.51		Gain of MoRF binding (P = 0.1202)
MVP		0.16
MPC		0.27
ClinPred		0.50	T
GERP RS		-3.4
PromoterAI		-0.11	Neutral
Varity_R		0.092
gMVP		0.28
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.42		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs778131898; hg19: chr11-2323404;