chr4-75957563-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• 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: Benign. The variant received -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.

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>G	p.Ser575Cys	missense	Exon 19 of 22	NP_060585.2
	SDAD1	NM_001288983.2		c.1613C>G	p.Ser538Cys	missense	Exon 18 of 21	NP_001275912.1
	SDAD1	NM_001288984.2		c.1433C>G	p.Ser478Cys	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>G	p.Ser575Cys	missense	Exon 19 of 22	ENSP00000348596.5
	SDAD1	ENST00000395710.5	TSL:1	n.*1580C>G		non_coding_transcript_exon	Exon 19 of 22	ENSP00000379060.1
	SDAD1	ENST00000395710.5	TSL:1	n.*1580C>G		3_prime_UTR	Exon 19 of 22	ENSP00000379060.1

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

GnomAD2 exomes AF: 0.335 AC: 84202 AN: 251444 AF XY: 0.350

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 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

African (AFR) AF: 0.247 AC: 8254 AN: 33480

American (AMR) AF: 0.162 AC: 7246 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 9385 AN: 26136

East Asian (EAS) AF: 0.0698 AC: 2772 AN: 39700

South Asian (SAS) AF: 0.443 AC: 38209 AN: 86254

European-Finnish (FIN) AF: 0.444 AC: 23707 AN: 53416

Middle Eastern (MID) AF: 0.339 AC: 1958 AN: 5768

European-Non Finnish (NFE) AF: 0.400 AC: 444564 AN: 1111840

Other (OTH) AF: 0.361 AC: 21773 AN: 60388

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

African (AFR) AF: 0.252 AC: 10468 AN: 41484

American (AMR) AF: 0.231 AC: 3537 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1269 AN: 3472

East Asian (EAS) AF: 0.0688 AC: 356 AN: 5178

South Asian (SAS) AF: 0.425 AC: 2041 AN: 4808

European-Finnish (FIN) AF: 0.452 AC: 4766 AN: 10542

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26969 AN: 67972

Other (OTH) AF: 0.320 AC: 673 AN: 2106

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 v4.9

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
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.1
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.18
Sift	Benign	0.047	D
Sift4G	Uncertain	0.060	T
Polyphen		0.60	P
Vest4		0.069
MPC		0.19
ClinPred		0.025	T
GERP RS		5.2
Varity_R		0.49
gMVP		0.14
Mutation Taster		=78/22	polymorphism (auto)

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; COSMIC: COSV62402827; COSMIC: COSV62402827;