Genetic Variant NM_019605.5:c.314G>A (chr1-210241580-G-A) – 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.314G>A(p.Arg105Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,526,780 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

SERTAD4
NM_019605.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.13

Publications

3 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.314G>A	p.Arg105Gln	missense	Exon 4 of 4	NP_062551.1	Q9NUC0
SERTAD4	NM_001375428.1		c.314G>A	p.Arg105Gln	missense	Exon 4 of 4	NP_001362357.1	Q9NUC0
SERTAD4	NM_001354173.2		c.291+1972G>A		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.314G>A	p.Arg105Gln	missense	Exon 4 of 4	ENSP00000355979.3	Q9NUC0
SERTAD4	ENST00000933764.1		c.314G>A	p.Arg105Gln	missense	Exon 5 of 5	ENSP00000603823.1
SERTAD4	ENST00000946958.1		c.314G>A	p.Arg105Gln	missense	Exon 4 of 4	ENSP00000617017.1

Frequencies

GnomAD3 genomes

AF:

0.0000274

AC:

AN:

146096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000257

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000689

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:

0.0000297

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000431

AC:

AN:

208750

AF XY:

0.0000353

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000503

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000217

AC:

AN:

1380596

Hom.:

Cov.:

AF XY:

0.0000250

AC XY:

AN XY:

679376

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30440

American (AMR)

AF:

0.000181

AC:

AN:

33080

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22836

East Asian (EAS)

AF:

0.00

AC:

AN:

37992

South Asian (SAS)

AF:

0.0000282

AC:

AN:

70828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51246

Middle Eastern (MID)

AF:

0.000396

AC:

AN:

5054

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

1072342

Other (OTH)

AF:

0.0000704

AC:

AN:

56778

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

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:

0.0000274

AC:

AN:

146184

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

70800

show subpopulations

African (AFR)

AF:

0.0000256

AC:

AN:

38994

American (AMR)

AF:

0.0000689

AC:

AN:

14522

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5024

South Asian (SAS)

AF:

0.00

AC:

AN:

4616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9122

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000297

AC:

AN:

67232

Other (OTH)

AF:

0.00

AC:

AN:

2030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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:

0.0000314

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

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

Pathogenic

0.76

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Pathogenic

0.35

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.66

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.3

PhyloP100

6.1

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.86

MVP

0.77

MPC

0.50

ClinPred

0.87

GERP RS

4.8

Varity_R

0.74

gMVP

0.79

Mutation Taster

=75/25

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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