Variant 4-75957683-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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. 14/20 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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.660

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 2654828.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDAD1	NM_018115.4 linkuse as main transcript	c.1604T>C	p.Met535Thr	missense_variant	19/22	ENST00000356260.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDAD1	ENST00000356260.10 linkuse as main transcript	c.1604T>C	p.Met535Thr	missense_variant	19/22	1	NM_018115.4	P1	Q9NVU7-1
SDAD1	ENST00000395710.5 linkuse as main transcript	c.*1460T>C		3_prime_UTR_variant, NMD_transcript_variant	19/22	1
SDAD1	ENST00000395711.8 linkuse as main transcript	c.1493T>C	p.Met498Thr	missense_variant	18/21	2

Frequencies

GnomAD3 genomes

AF:

0.00458

AC:

697

AN:

152184

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00523

AC:

1313

AN:

250996

Hom.:

AF XY:

0.00507

AC XY:

689

AN XY:

135808

show subpopulations

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 SAS exome

AF:

0.00101

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.:

Cov.:

AF XY:

0.00513

AC XY:

3731

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.000693

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00130

Gnomad4 FIN exome

AF:

0.0261

Gnomad4 NFE exome

AF:

0.00500

Gnomad4 OTH exome

AF:

0.00402

GnomAD4 genome

AF:

0.00458

AC:

697

AN:

152302

Hom.:

Cov.:

AF XY:

0.00490

AC XY:

365

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0250

Gnomad4 NFE

AF:

0.00560

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00510

Hom.:

Bravo

AF:

0.00251

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00453

AC:

ExAC

AF:

0.00529

AC:

642

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00583

EpiControl

AF:

0.00462

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

SDAD1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.64

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

LIST_S2

Benign

0.49

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.060

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

0.19

N;N

REVEL

Benign

0.010

Sift

Benign

0.71

T;T

Sift4G

Benign

0.59

T;T

Polyphen

0.0

B;B

Vest4

0.055

MVP

0.10

MPC

0.061

ClinPred

0.0030

GERP RS

-0.15

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.047

gMVP

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over