4-75957563-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018115.4(SDAD1):c.1724C>A(p.Ser575Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. S575C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SDAD1 NM_018115.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.09

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2159321).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDAD1	NM_018115.4	c.1724C>A	p.Ser575Tyr	missense_variant	19/22	ENST00000356260.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDAD1	ENST00000356260.10	c.1724C>A	p.Ser575Tyr	missense_variant	19/22	1	NM_018115.4	P1
SDAD1	ENST00000395710.5	c.*1580C>A		3_prime_UTR_variant, NMD_transcript_variant	19/22	1
SDAD1	ENST00000395711.8	c.1613C>A	p.Ser538Tyr	missense_variant	18/21	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.012	T;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Uncertain	0.32	D
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	0.65	P;P
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.85	N;N
REVEL	Benign	0.12
Sift	Benign	0.047	D;T
Sift4G	Benign	0.10	T;T
Polyphen		0.60	P;P
Vest4		0.23
MutPred		0.38		Loss of phosphorylation at S575 (P = 0.0344);.;
MVP		0.95
MPC		0.11
ClinPred		0.75	D
GERP RS		5.2
Varity_R		0.45
gMVP		0.16

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

LitVar

Other links and lift over

dbSNP: rs2242471; hg19: chr4-76878716;