rs114534142

Variant names:

• chr4-75957683-A-G
• rs114534142
• NM_018115.4:c.1604T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_018115.4(SDAD1):​c.1604T>C​(p.Met535Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00503 in 1,614,188 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (45 hom.)
• Consequence: SDAD1 NM_018115.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.660
• Publications: 5 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017833412).
• BP6: Variant 4-75957683-A-G is Benign according to our data. Variant chr4-75957683-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2654828.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

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.1604T>C	p.Met535Thr	missense	Exon 19 of 22	NP_060585.2	Q9NVU7-1
	SDAD1	NM_001288983.2		c.1493T>C	p.Met498Thr	missense	Exon 18 of 21	NP_001275912.1	E7EW05
	SDAD1	NM_001288984.2		c.1313T>C	p.Met438Thr	missense	Exon 19 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.1604T>C	p.Met535Thr	missense	Exon 19 of 22	ENSP00000348596.5	Q9NVU7-1
	SDAD1	ENST00000395710.5	TSL:1	n.*1460T>C		non_coding_transcript_exon	Exon 19 of 22	ENSP00000379060.1	F8W8T7
	SDAD1	ENST00000395710.5	TSL:1	n.*1460T>C		3_prime_UTR	Exon 19 of 22	ENSP00000379060.1	F8W8T7

Frequencies

GnomAD3 genomes AF: 0.00458 AC: 697 AN: 152184 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0250

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00560

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00523 AC: 1313 AN: 250996 AF XY: 0.00507

Gnomad AFR exome AF: 0.000437

Gnomad AMR exome AF: 0.000578

Gnomad ASJ exome AF: 0.00218

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0265

Gnomad NFE exome AF: 0.00554

Gnomad OTH exome AF: 0.00508

GnomAD4 exome AF: 0.00507 AC: 7417 AN: 1461886 Hom.: 45 Cov.: 35 AF XY: 0.00513 AC XY: 3731 AN XY: 727244

African (AFR) AF: 0.000687 AC: 23 AN: 33480

American (AMR) AF: 0.000693 AC: 31 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00142 AC: 37 AN: 26136

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

South Asian (SAS) AF: 0.00130 AC: 112 AN: 86258

European-Finnish (FIN) AF: 0.0261 AC: 1392 AN: 53416

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5768

European-Non Finnish (NFE) AF: 0.00500 AC: 5565 AN: 1112008

Other (OTH) AF: 0.00402 AC: 243 AN: 60396

GnomAD4 genome AF: 0.00458 AC: 697 AN: 152302 Hom.: 6 Cov.: 32 AF XY: 0.00490 AC XY: 365 AN XY: 74466

African (AFR) AF: 0.000601 AC: 25 AN: 41582

American (AMR) AF: 0.000915 AC: 14 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4822

European-Finnish (FIN) AF: 0.0250 AC: 265 AN: 10596

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

European-Non Finnish (NFE) AF: 0.00560 AC: 381 AN: 68020

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00501 Hom.: 14

Bravo AF: 0.00251

TwinsUK AF: 0.00378 AC: 14

ALSPAC AF: 0.00493 AC: 19

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00453 AC: 39

ExAC AF: 0.00529 AC: 642

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00583

EpiControl AF: 0.00462

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.7
DANN	Benign	0.48
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.060	N
PhyloP100		0.66
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.010
Sift	Benign	0.71	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.055
MVP		0.10
MPC		0.061
ClinPred		0.0030	T
GERP RS		-0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.047
gMVP		0.11
Mutation Taster		=99/1	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: rs114534142; hg19: chr4-76878836;