Genetic Variant NM_019605.5:c.357C>G (chr1-210241623-C-G) – 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_019605.5(SERTAD4):c.357C>G(p.Ile119Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,608,074 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

SERTAD4
NM_019605.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.262

Publications

0 publications found

Variant links:

Genes affected

SERTAD4 (HGNC:25236): (SERTA domain containing 4) Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SERTAD4 links:

Genome browser will be placed here

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_019605.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERTAD4	NM_019605.5	MANE Select	c.357C>G	p.Ile119Met	missense	Exon 4 of 4	NP_062551.1	Q9NUC0
SERTAD4	NM_001375428.1		c.357C>G	p.Ile119Met	missense	Exon 4 of 4	NP_001362357.1	Q9NUC0
SERTAD4	NM_001354173.2		c.291+2015C>G		intron	N/A	NP_001341102.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERTAD4	ENST00000367012.4	TSL:1 MANE Select	c.357C>G	p.Ile119Met	missense	Exon 4 of 4	ENSP00000355979.3	Q9NUC0
SERTAD4	ENST00000933764.1		c.357C>G	p.Ile119Met	missense	Exon 5 of 5	ENSP00000603823.1
SERTAD4	ENST00000946958.1		c.357C>G	p.Ile119Met	missense	Exon 4 of 4	ENSP00000617017.1

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

148592

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000360

AC:

AN:

250298

AF XY:

0.0000222

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:

0.0000795

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000445

AC:

AN:

1459482

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

725948

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33384

American (AMR)

AF:

0.00

AC:

AN:

44562

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26030

East Asian (EAS)

AF:

0.00

AC:

AN:

39626

South Asian (SAS)

AF:

0.00

AC:

AN:

85948

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53198

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.0000540

AC:

AN:

1110762

Other (OTH)

AF:

0.0000830

AC:

AN:

60226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

0.0000135

AC:

AN:

148592

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

72190

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40022

American (AMR)

AF:

0.00

AC:

AN:

14764

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5056

South Asian (SAS)

AF:

0.00

AC:

AN:

4712

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9694

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67628

Other (OTH)

AF:

0.00

AC:

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.0000843

Hom.:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

0.41

BayesDel_addAF

Uncertain

0.084

BayesDel_noAF

Uncertain

0.080

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

Eigen

Benign

0.17

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.81

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.73

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.94

PhyloP100

0.26

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.52

Sift

Benign

0.082

Sift4G

Benign

0.13

Polyphen

1.0

Vest4

0.80

MutPred

0.64

Gain of catalytic residue at I119 (P = 0.0159)

MVP

0.55

MPC

0.47

ClinPred

0.29

GERP RS

0.37

Varity_R

0.36

gMVP

0.36

Mutation Taster

=67/33

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

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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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over