chr4-75982022-T-C

Position:

• chr4-75982022-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001288984.2(SDAD1):​c.-261A>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000000688 in 1,454,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SDAD1 NM_001288984.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.26

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35693744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDAD1	NM_018115.4	c.106A>G	p.Asn36Asp	missense_variant	2/22	ENST00000356260.10	NP_060585.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDAD1	ENST00000356260.10	c.106A>G	p.Asn36Asp	missense_variant	2/22	1	NM_018115.4	ENSP00000348596.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454182 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 723596

Gnomad4 AFR exome AF: 0.0000301

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

Bravo AF: 0.00000378

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

Apr 25, 2022

The c.106A>G (p.N36D) alteration is located in exon 2 (coding exon 2) of the SDAD1 gene. This alteration results from a A to G substitution at nucleotide position 106, causing the asparagine (N) at amino acid position 36 to be replaced by an aspartic acid (D). 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	0.11
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	0.0014
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.86	D;D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.10
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.023	D;D
Polyphen		0.14	B;B
Vest4		0.41
MutPred		0.27		Gain of phosphorylation at Y38 (P = 0.1041);Gain of phosphorylation at Y38 (P = 0.1041);
MVP		0.73
MPC		0.062
ClinPred		0.83	D
GERP RS		4.7
Varity_R		0.24
gMVP		0.27

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: rs1730555372; hg19: chr4-76903175;