4-75960161-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018115.4(SDAD1):c.1388G>C(p.Arg463Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SDAD1 NM_018115.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.50

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16820744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDAD1	NM_018115.4	c.1388G>C	p.Arg463Thr	missense_variant	17/22	ENST00000356260.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDAD1	ENST00000356260.10	c.1388G>C	p.Arg463Thr	missense_variant	17/22	1	NM_018115.4	P1
SDAD1	ENST00000395710.5	c.*1244G>C		3_prime_UTR_variant, NMD_transcript_variant	17/22	1
SDAD1	ENST00000395711.8	c.1277G>C	p.Arg426Thr	missense_variant	16/21	2
SDAD1	ENST00000513089.5	n.694G>C		non_coding_transcript_exon_variant	9/9	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456964 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724776

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2022

The c.1388G>C (p.R463T) alteration is located in exon 17 (coding exon 17) of the SDAD1 gene. This alteration results from a G to C substitution at nucleotide position 1388, causing the arginine (R) at amino acid position 463 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	23
Dann	Benign	0.96
DEOGEN2	Benign	0.017	T;.
Eigen	Benign	0.032
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;.
MutationTaster	Benign	0.82	D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.044
Sift	Benign	0.14	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.38	B;B
Vest4		0.38
MutPred		0.46		Gain of phosphorylation at R463 (P = 0.0673);.;
MVP		0.36
MPC		0.11
ClinPred		0.74	D
GERP RS		4.8
Varity_R		0.30
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-76881314;