Genetic Variant NM_018115.4:c.1982G>C (chr4-75956009-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_018115.4(SDAD1):c.1982G>C(p.Arg661Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000346 in 1,446,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R661Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

SDAD1
NM_018115.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.74

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.77

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.1982G>C	p.Arg661Pro	missense	Exon 21 of 22	NP_060585.2	Q9NVU7-1
SDAD1	NM_001288983.2		c.1871G>C	p.Arg624Pro	missense	Exon 20 of 21	NP_001275912.1	E7EW05
SDAD1	NM_001288984.2		c.1691G>C	p.Arg564Pro	missense	Exon 21 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.1982G>C	p.Arg661Pro	missense	Exon 21 of 22	ENSP00000348596.5	Q9NVU7-1
SDAD1	ENST00000395710.5	TSL:1	n.*1838G>C		non_coding_transcript_exon	Exon 21 of 22	ENSP00000379060.1	F8W8T7
SDAD1	ENST00000395710.5	TSL:1	n.*1838G>C		3_prime_UTR	Exon 21 of 22	ENSP00000379060.1	F8W8T7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000346

AC:

AN:

1446292

Hom.:

Cov.:

AF XY:

0.00000695

AC XY:

AN XY:

719096

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32178

American (AMR)

AF:

0.00

AC:

AN:

40562

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25630

East Asian (EAS)

AF:

0.00

AC:

AN:

39406

South Asian (SAS)

AF:

0.00

AC:

AN:

82360

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4856

European-Non Finnish (NFE)

AF:

0.00000451

AC:

AN:

1108342

Other (OTH)

AF:

0.00

AC:

AN:

59658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.60

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.051

MetaRNN

Pathogenic

0.77

MetaSVM

Benign

-0.76

MutationAssessor

Pathogenic

3.4

PhyloP100

5.7

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-4.0

REVEL

Uncertain

0.45

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0050

Polyphen

0.98

Vest4

0.69

MutPred

0.56

Gain of glycosylation at R661 (P = 0.037)

MVP

0.59

MPC

0.36

ClinPred

0.99

GERP RS

4.7

Varity_R

0.96

gMVP

0.35

Mutation Taster

=2/98

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over