Genetic Variant SDAD1:p.Asp493Asn (chr4-75960072-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018115.4(SDAD1):c.1477G>A(p.Asp493Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D493Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SDAD1
NM_018115.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.07

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08873552).

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.1477G>A	p.Asp493Asn	missense	Exon 17 of 22	NP_060585.2	Q9NVU7-1
SDAD1	NM_001288983.2		c.1366G>A	p.Asp456Asn	missense	Exon 16 of 21	NP_001275912.1	E7EW05
SDAD1	NM_001288984.2		c.1186G>A	p.Asp396Asn	missense	Exon 17 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.1477G>A	p.Asp493Asn	missense	Exon 17 of 22	ENSP00000348596.5	Q9NVU7-1
SDAD1	ENST00000395710.5	TSL:1	n.*1333G>A		non_coding_transcript_exon	Exon 17 of 22	ENSP00000379060.1	F8W8T7
SDAD1	ENST00000395710.5	TSL:1	n.*1333G>A		3_prime_UTR	Exon 17 of 22	ENSP00000379060.1	F8W8T7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000407

AC:

AN:

245558

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:

0.00000893

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454232

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33074

American (AMR)

AF:

0.00

AC:

AN:

43140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25908

East Asian (EAS)

AF:

0.00

AC:

AN:

39652

South Asian (SAS)

AF:

0.00

AC:

AN:

84788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110452

Other (OTH)

AF:

0.00

AC:

AN:

60032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0083

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.76

M_CAP

Benign

0.0055

MetaRNN

Benign

0.089

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PhyloP100

2.1

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.1

REVEL

Benign

0.044

Sift

Benign

0.11

Sift4G

Benign

0.18

Polyphen

0.0070

Vest4

0.12

MutPred

0.53

Loss of helix (P = 0.0558)

MVP

0.17

MPC

0.057

ClinPred

0.068

GERP RS

3.0

Varity_R

0.13

gMVP

0.13

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over