dbSNP rs747108765: TMA16:p.Asn49Lys (chr4-163512852-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_018352.3(TMA16):c.147C>A(p.Asn49Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,606,656 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

TMA16
NM_018352.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.265

Publications

1 publications found

Variant links:

Genes affected

TMA16 (HGNC:25638): (translation machinery associated 16 homolog) Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TMA16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30785316).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018352.3. 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
	TMA16	NM_018352.3	MANE Select	c.147C>A	p.Asn49Lys	missense	Exon 3 of 7	NP_060822.2	Q96EY4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMA16	ENST00000358572.10	TSL:1 MANE Select	c.147C>A	p.Asn49Lys	missense	Exon 3 of 7	ENSP00000351380.5	Q96EY4
TMA16	ENST00000509657.5	TSL:5	c.261C>A	p.Asn87Lys	missense	Exon 3 of 7	ENSP00000425347.1	H0Y9X1
TMA16	ENST00000911660.1		c.147C>A	p.Asn49Lys	missense	Exon 3 of 7	ENSP00000581719.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000806

AC:

AN:

248266

AF XY:

0.00000742

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:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1454500

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723214

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33378

American (AMR)

AF:

0.00

AC:

AN:

44538

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25892

East Asian (EAS)

AF:

0.00

AC:

AN:

39554

South Asian (SAS)

AF:

0.00

AC:

AN:

85114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

1107130

Other (OTH)

AF:

0.00

AC:

AN:

59998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

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:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74330

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000241

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000329

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

Uncertain

0.37

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.084

Eigen

Benign

0.048

Eigen_PC

Benign

0.018

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.79

M_CAP

Benign

0.035

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.9

PhyloP100

-0.27

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.21

Sift

Uncertain

0.023

Sift4G

Benign

0.092

Polyphen

0.29

Vest4

0.22

MutPred

0.51

Loss of catalytic residue at N49 (P = 0.0264)

MVP

0.40

MPC

0.13

ClinPred

0.89

GERP RS

1.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.46

gMVP

0.33

Mutation Taster

=70/30

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over