Genetic Variant NM_018986.5:c.13C>T (chr4-8205207-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018986.5(SH3TC1):c.13C>T(p.Pro5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,386,900 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. P5L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SH3TC1
NM_018986.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.207

Publications

0 publications found

Variant links:

Genes affected

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

SH3TC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06397036).

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.13C>T	p.Pro5Ser	missense	Exon 2 of 18	NP_061859.4
SH3TC1	NM_001410712.1		c.13C>T	p.Pro5Ser	missense	Exon 2 of 18	NP_001397641.1	A0A804HI81
SH3TC1	NM_001318480.2		c.-299C>T		5_prime_UTR	Exon 2 of 18	NP_001305409.2	H0YA34

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH3TC1	ENST00000245105.8	TSL:2 MANE Select	c.13C>T	p.Pro5Ser	missense	Exon 2 of 18	ENSP00000245105.3	Q8TE82
SH3TC1	ENST00000382521.7	TSL:1	c.13C>T	p.Pro5Ser	missense	Exon 2 of 3	ENSP00000371961.3	Q6NVH2
SH3TC1	ENST00000502669.5	TSL:1	n.13C>T		non_coding_transcript_exon	Exon 2 of 15	ENSP00000425970.1	D6RI07

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000690

AC:

AN:

144830

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:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.21e-7

AC:

AN:

1386900

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

683782

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31086

American (AMR)

AF:

0.00

AC:

AN:

33506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24146

East Asian (EAS)

AF:

0.00

AC:

AN:

35712

South Asian (SAS)

AF:

0.00

AC:

AN:

77490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48424

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4274

European-Non Finnish (NFE)

AF:

9.30e-7

AC:

AN:

1074916

Other (OTH)

AF:

0.00

AC:

AN:

57346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

0.077

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.41

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.058

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.54

M_CAP

Benign

0.0098

MetaRNN

Benign

0.064

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

-0.21

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.13

Sift

Benign

0.12

Sift4G

Pathogenic

0.0

Polyphen

0.029

Vest4

0.079

MutPred

0.14

Gain of glycosylation at T8 (P = 0.0977)

MVP

0.38

MPC

0.027

ClinPred

0.047

GERP RS

-1.2

PromoterAI

0.028

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.083

gMVP

0.12

Mutation Taster

=263/37

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over