Genetic Variant NM_018986.5:c.14C>T (chr4-8205208-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018986.5(SH3TC1):c.14C>T(p.Pro5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000546 in 1,539,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 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. P5S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

SH3TC1
NM_018986.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.32

Publications

0 publications found

Variant links:

Genes affected

SH3TC1 (HGNC:26009): (SH3 domain and tetratricopeptide repeats 1)

SH3TC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.086913764).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018986.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH3TC1	NM_018986.5	MANE Select	c.14C>T	p.Pro5Leu	missense	Exon 2 of 18	NP_061859.4
SH3TC1	NM_001318480.2		c.-298C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 18	NP_001305409.2	H0YA34
SH3TC1	NM_001410712.1		c.14C>T	p.Pro5Leu	missense	Exon 2 of 18	NP_001397641.1	A0A804HI81

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH3TC1	ENST00000245105.8	TSL:2 MANE Select	c.14C>T	p.Pro5Leu	missense	Exon 2 of 18	ENSP00000245105.3	Q8TE82
SH3TC1	ENST00000382521.7	TSL:1	c.14C>T	p.Pro5Leu	missense	Exon 2 of 3	ENSP00000371961.3	Q6NVH2
SH3TC1	ENST00000502669.5	TSL:1	n.14C>T		non_coding_transcript_exon	Exon 2 of 15	ENSP00000425970.1	D6RI07

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000482

AC:

AN:

145218

AF XY:

0.0000653

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:

0.0000671

Gnomad NFE exome

AF:

0.000109

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000562

AC:

AN:

1387370

Hom.:

Cov.:

AF XY:

0.0000541

AC XY:

AN XY:

684074

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31102

American (AMR)

AF:

0.0000298

AC:

AN:

33572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24198

East Asian (EAS)

AF:

0.00

AC:

AN:

35716

South Asian (SAS)

AF:

0.00

AC:

AN:

77536

European-Finnish (FIN)

AF:

0.0000413

AC:

AN:

48454

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4284

European-Non Finnish (NFE)

AF:

0.0000679

AC:

AN:

1075128

Other (OTH)

AF:

0.0000349

AC:

AN:

57380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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

AF:

0.0000394

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000932

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000565

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

0.086

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.40

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.071

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.61

M_CAP

Benign

0.011

MetaRNN

Benign

0.087

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PhyloP100

-1.3

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.12

Sift

Benign

0.032

Sift4G

Pathogenic

0.0

Polyphen

0.013

Vest4

0.051

MVP

0.50

MPC

0.027

ClinPred

0.051

GERP RS

-1.9

PromoterAI

0.021

Neutral

(source)

Varity_R

0.087

gMVP

0.12

Mutation Taster

=297/3

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over