Genetic Variant NM_018115.4:c.1492G>A (chr4-75957933-C-T) – 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_018115.4(SDAD1):c.1492G>A(p.Glu498Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,322 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SDAD1
NM_018115.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.27

Publications

0 publications found

Variant links:

Genes affected

SDAD1 (HGNC:25537): (SDA1 domain containing 1) Predicted to be involved in ribosomal large subunit biogenesis and ribosomal large subunit export from nucleus. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SDAD1 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_018115.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SDAD1	NM_018115.4	MANE Select	c.1492G>A	p.Glu498Lys	missense	Exon 18 of 22	NP_060585.2	Q9NVU7-1
SDAD1	NM_001288983.2		c.1381G>A	p.Glu461Lys	missense	Exon 17 of 21	NP_001275912.1	E7EW05
SDAD1	NM_001288984.2		c.1201G>A	p.Glu401Lys	missense	Exon 18 of 22	NP_001275913.1	Q9NVU7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SDAD1	ENST00000356260.10	TSL:1 MANE Select	c.1492G>A	p.Glu498Lys	missense	Exon 18 of 22	ENSP00000348596.5	Q9NVU7-1
SDAD1	ENST00000395710.5	TSL:1	n.*1348G>A		non_coding_transcript_exon	Exon 18 of 22	ENSP00000379060.1	F8W8T7
SDAD1	ENST00000395710.5	TSL:1	n.*1348G>A		3_prime_UTR	Exon 18 of 22	ENSP00000379060.1	F8W8T7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251418

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460322

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726466

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33424

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86186

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4530

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111940

Other (OTH)

AF:

0.00

AC:

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

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

0.26

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.73

MetaSVM

Benign

-0.95

MutationAssessor

Pathogenic

3.5

PhyloP100

5.3

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.7

REVEL

Benign

0.25

Sift

Benign

0.18

Sift4G

Benign

0.10

Polyphen

0.95

Vest4

0.78

MutPred

0.58

Gain of ubiquitination at E498 (P = 0.006)

MVP

0.47

MPC

0.24

ClinPred

0.93

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.39

gMVP

0.32

Mutation Taster

=43/57

disease causing

(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