rs542154908

Variant names:

• chr4-75990821-G-C
• rs542154908
• NM_018115.4:c.21C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018115.4(SDAD1):​c.21C>G​(p.Asn7Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,614,102 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: SDAD1 NM_018115.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54
• Publications: 0 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]

SDAD1-AS1 (HGNC:41106): (SDAD1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.21C>G	p.Asn7Lys	missense	Exon 1 of 22	NP_060585.2	Q9NVU7-1
	SDAD1	NM_001288983.2		c.21C>G	p.Asn7Lys	missense	Exon 1 of 21	NP_001275912.1	E7EW05
	SDAD1	NM_001288984.2		c.-346C>G		5_prime_UTR	Exon 1 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.21C>G	p.Asn7Lys	missense	Exon 1 of 22	ENSP00000348596.5	Q9NVU7-1
	SDAD1	ENST00000395710.5	TSL:1	n.21C>G		non_coding_transcript_exon	Exon 1 of 22	ENSP00000379060.1	F8W8T7
	SDAD1-AS1	ENST00000501239.2	TSL:1	n.177-5285G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000401 AC: 10 AN: 249546 AF XY: 0.0000591

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000260 AC: 38 AN: 1461842 Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29 AN XY: 727218

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000371 AC: 32 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152260 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74426

African (AFR) AF: 0.00 AC: 0 AN: 41548

American (AMR) AF: 0.00 AC: 0 AN: 15296

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000331 AC: 4

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	Pathogenic	0.59
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Uncertain	0.26	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.5
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.25		Gain of methylation at N7 (P = 0.0059)
MVP		0.83
MPC		0.19
ClinPred		0.86	D
GERP RS		5.1
PromoterAI		0.041	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.42
Mutation Taster		=27/73	disease causing

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: rs542154908; hg19: chr4-76911974;