Genetic Variant THSD7B:p.Leu318Phe (chr2-137094874-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001316349.2(THSD7B):c.952C>T(p.Leu318Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000618 in 1,457,386 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 in silico tools predict 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

THSD7B
NM_001316349.2 missense, splice_region

Scores

Splicing: ADA: 0.0009254

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

Publications

0 publications found

Variant links:

Genes affected

THSD7B (HGNC:29348): (thrombospondin type 1 domain containing 7B) Predicted to be involved in actin cytoskeleton reorganization. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

THSD7B links:

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ACMG classification

Classification was made for transcript

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_001316349.2. 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
	THSD7B	NM_001316349.2	MANE Select	c.952C>T	p.Leu318Phe	missense splice_region	Exon 4 of 28	NP_001303278.1	Q9C0I4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD7B	ENST00000409968.6	TSL:5 MANE Select	c.952C>T	p.Leu318Phe	missense splice_region	Exon 4 of 28	ENSP00000387145.1	Q9C0I4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000404

AC:

AN:

247310

AF XY:

0.00

show subpopulations

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:

0.0000465

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000618

AC:

AN:

1457386

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

724356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33308

American (AMR)

AF:

0.00

AC:

AN:

44408

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25988

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39580

South Asian (SAS)

AF:

0.00

AC:

AN:

85750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1109084

Other (OTH)

AF:

0.0000665

AC:

AN:

60150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000828

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.68

M_CAP

Benign

0.0096

MetaRNN

Uncertain

0.46

MetaSVM

Benign

-1.0

PhyloP100

1.1

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.2

REVEL

Benign

0.13

Sift

Benign

0.43

Sift4G

Benign

0.23

Polyphen

1.0

Vest4

0.26

MutPred

0.48

Loss of disorder (P = 0.2433)

MVP

0.24

MPC

0.63

ClinPred

0.86

GERP RS

4.4

gMVP

0.49

Mutation Taster

=49/51

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00093

dbscSNV1_RF

Benign

0.0040

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over