rs2242471

chr4-75957563-G-Cchr4-75957563-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018115.4(SDAD1):c.1724C>G(p.Ser575Cys) variant causes a missense change. The variant allele was found at a frequency of 0.377 in 1,613,754 control chromosomes in the GnomAD database, including 120,091 homozygotes. 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.33 (9184 hom., cov: 32)
  • Exomes 𝑓: 0.38 (110907 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003446132).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDAD1	NM_018115.4	c.1724C>G	p.Ser575Cys	missense_variant	19/22	ENST00000356260.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDAD1	ENST00000356260.10	c.1724C>G	p.Ser575Cys	missense_variant	19/22	1	NM_018115.4	P1
SDAD1	ENST00000395710.5	c.*1580C>G		3_prime_UTR_variant, NMD_transcript_variant	19/22	1
SDAD1	ENST00000395711.8	c.1613C>G	p.Ser538Cys	missense_variant	18/21	2

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50333 AN: 151932 Hom.: 9191 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.0688

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.319

GnomAD3 exomes AF: 0.335 AC: 84202 AN: 251444 Hom.: 16170 AF XY: 0.350 AC XY: 47532 AN XY: 135892

Gnomad AFR exome AF: 0.244

Gnomad AMR exome AF: 0.152

Gnomad ASJ exome AF: 0.360

Gnomad EAS exome AF: 0.0580

Gnomad SAS exome AF: 0.448

Gnomad FIN exome AF: 0.440

Gnomad NFE exome AF: 0.396

Gnomad OTH exome AF: 0.334

GnomAD4 exome AF: 0.382 AC: 557868 AN: 1461704 Hom.: 110907 Cov.: 53 AF XY: 0.384 AC XY: 279112 AN XY: 727162

Gnomad4 AFR exome AF: 0.247

Gnomad4 AMR exome AF: 0.162

Gnomad4 ASJ exome AF: 0.359

Gnomad4 EAS exome AF: 0.0698

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.444

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.361

GnomAD4 genome AF: 0.331 AC: 50326 AN: 152050 Hom.: 9184 Cov.: 32 AF XY: 0.331 AC XY: 24606 AN XY: 74298

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.0688

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.320

Alfa AF: 0.343 Hom.: 2877

Bravo AF: 0.304

TwinsUK AF: 0.389 AC: 1441

ALSPAC AF: 0.392 AC: 1512

ESP6500AA AF: 0.251 AC: 1104

ESP6500EA AF: 0.391 AC: 3365

ExAC AF: 0.341 AC: 41396

Asia WGS AF: 0.270 AC: 942 AN: 3478

EpiCase AF: 0.393

EpiControl AF: 0.387

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.35
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.013	T;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D;D
MetaRNN	Benign	0.0034	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	0.78	P;P
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.18
Sift	Benign	0.047	D;T
Sift4G	Uncertain	0.060	T;T
Polyphen		0.60	P;P
Vest4		0.069
MPC		0.19
ClinPred		0.025	T
GERP RS		5.2
Varity_R		0.49
gMVP		0.14

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; COSMIC: COSV62402827; COSMIC: COSV62402827;