NM_018115.4:c.1724C>A

Variant names:

• chr4-75957563-G-T
• rs2242471
• NM_018115.4:c.1724C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SDAD1 NM_018115.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.09
• Publications: 41 publications found

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

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=0.2159321).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDAD1	NM_018115.4	MANE Select	c.1724C>A	p.Ser575Tyr	missense	Exon 19 of 22	NP_060585.2
	SDAD1	NM_001288983.2		c.1613C>A	p.Ser538Tyr	missense	Exon 18 of 21	NP_001275912.1
	SDAD1	NM_001288984.2		c.1433C>A	p.Ser478Tyr	missense	Exon 19 of 22	NP_001275913.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDAD1	ENST00000356260.10	TSL:1 MANE Select	c.1724C>A	p.Ser575Tyr	missense	Exon 19 of 22	ENSP00000348596.5
	SDAD1	ENST00000395710.5	TSL:1	n.*1580C>A		non_coding_transcript_exon	Exon 19 of 22	ENSP00000379060.1
	SDAD1	ENST00000395710.5	TSL:1	n.*1580C>A		3_prime_UTR	Exon 19 of 22	ENSP00000379060.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2877

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.22	T
MetaSVM	Uncertain	0.32	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.1
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.12
Sift	Benign	0.047	D
Sift4G	Benign	0.10	T
Polyphen		0.60	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
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs2242471; hg19: chr4-76878716;