4-75956009-C-T

Variant names:

• chr4-75956009-C-T
• rs139040292
• NM_018115.4:c.1982G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018115.4(SDAD1):​c.1982G>A​(p.Arg661Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000238 in 1,598,602 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R661R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (1 hom.)
• Consequence: SDAD1 NM_018115.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.74
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1950694).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDAD1	NM_018115.4	MANE Select	c.1982G>A	p.Arg661Gln	missense	Exon 21 of 22	NP_060585.2	Q9NVU7-1
	SDAD1	NM_001288983.2		c.1871G>A	p.Arg624Gln	missense	Exon 20 of 21	NP_001275912.1	E7EW05
	SDAD1	NM_001288984.2		c.1691G>A	p.Arg564Gln	missense	Exon 21 of 22	NP_001275913.1	Q9NVU7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDAD1	ENST00000356260.10	TSL:1 MANE Select	c.1982G>A	p.Arg661Gln	missense	Exon 21 of 22	ENSP00000348596.5	Q9NVU7-1
	SDAD1	ENST00000395710.5	TSL:1	n.*1838G>A		non_coding_transcript_exon	Exon 21 of 22	ENSP00000379060.1	F8W8T7
	SDAD1	ENST00000395710.5	TSL:1	n.*1838G>A		3_prime_UTR	Exon 21 of 22	ENSP00000379060.1	F8W8T7

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000298 AC: 7 AN: 235266 AF XY: 0.0000315

Gnomad AFR exome AF: 0.000253

Gnomad AMR exome AF: 0.0000334

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000187 AC: 27 AN: 1446290 Hom.: 1 Cov.: 31 AF XY: 0.0000223 AC XY: 16 AN XY: 719096

African (AFR) AF: 0.000155 AC: 5 AN: 32178

American (AMR) AF: 0.0000493 AC: 2 AN: 40562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25630

East Asian (EAS) AF: 0.00 AC: 0 AN: 39406

South Asian (SAS) AF: 0.0000607 AC: 5 AN: 82358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4856

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1108342

Other (OTH) AF: 0.0000503 AC: 3 AN: 59658

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74482

African (AFR) AF: 0.000216 AC: 9 AN: 41578

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000986 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.7
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.12
Sift	Benign	0.10	T
Sift4G	Benign	0.20	T
Polyphen		0.63	P
Vest4		0.50
MVP		0.37
MPC		0.089
ClinPred		0.071	T
GERP RS		4.7
Varity_R		0.37
gMVP		0.23
Mutation Taster		=96/4	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: rs139040292; hg19: chr4-76877162; COSMIC: COSV62403787; COSMIC: COSV62403787;