NM_018115.4:c.2056A>C

Variant names:

• chr4-75950758-T-G
• rs1355243904
• NM_018115.4:c.2056A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018115.4(SDAD1):​c.2056A>C​(p.Met686Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000625 in 1,440,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M686V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SDAD1 NM_018115.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18
• 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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07912174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDAD1	NM_018115.4	c.2056A>C	p.Met686Leu	missense_variant	Exon 22 of 22	ENST00000356260.10	NP_060585.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDAD1	ENST00000356260.10	c.2056A>C	p.Met686Leu	missense_variant	Exon 22 of 22	1	NM_018115.4	ENSP00000348596.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000625 AC: 9 AN: 1440302 Hom.: 0 Cov.: 27 AF XY: 0.00000699 AC XY: 5 AN XY: 715008

African (AFR) AF: 0.00 AC: 0 AN: 33226

American (AMR) AF: 0.00 AC: 0 AN: 44302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25678

East Asian (EAS) AF: 0.00 AC: 0 AN: 39404

South Asian (SAS) AF: 0.00 AC: 0 AN: 84730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5604

European-Non Finnish (NFE) AF: 0.00000822 AC: 9 AN: 1095108

Other (OTH) AF: 0.00 AC: 0 AN: 59312

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Benign	0.87
DEOGEN2	Benign	0.012	T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.4	N;.
PhyloP100		2.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.12
Sift	Benign	0.47	T;T
Sift4G	Benign	0.68	T;T
Polyphen		0.026	B;B
Vest4		0.45
MutPred		0.33		Loss of helix (P = 0.1299);.;
MVP		0.32
MPC		0.052
ClinPred		0.36	T
GERP RS		4.3
Varity_R		0.099
gMVP		0.10
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1355243904; hg19: chr4-76871911;