rs6564956

Variant names:

• chr16-82000830-C-G
• rs6564956
• NM_145168.3:c.29G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-82000830-C-G
• chr16-82000830-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145168.3(SDR42E1):​c.29G>C​(p.Ser10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0277 in 1,612,950 control chromosomes in the GnomAD database, including 5,071 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (2577 hom., cov: 32)
  • Exomes 𝑓: 0.020 (2494 hom.)
• Consequence: SDR42E1 NM_145168.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.528
• Publications: 10 publications found

Genes affected

SDR42E1 (HGNC:29834): (short chain dehydrogenase/reductase family 42E, member 1) Predicted to enable oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. Predicted to be involved in steroid biosynthetic process. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0076619387).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145168.3. 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
	SDR42E1	NM_145168.3	MANE Select	c.29G>C	p.Ser10Thr	missense	Exon 2 of 3	NP_660151.2	Q8WUS8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDR42E1	ENST00000328945.7	TSL:1 MANE Select	c.29G>C	p.Ser10Thr	missense	Exon 2 of 3	ENSP00000332407.4	Q8WUS8
	SDR42E1	ENST00000532128.5	TSL:5	c.-98G>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	ENSP00000434529.1	E9PQ06
	SDR42E1	ENST00000867081.1		c.29G>C	p.Ser10Thr	missense	Exon 2 of 3	ENSP00000537140.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16107 AN: 152112 Hom.: 2558 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0459

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.0429

Gnomad SAS AF: 0.0728

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00651

Gnomad OTH AF: 0.0737

GnomAD2 exomes AF: 0.0385 AC: 9574 AN: 248908 AF XY: 0.0341

Gnomad AFR exome AF: 0.344

Gnomad AMR exome AF: 0.0229

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.0391

Gnomad FIN exome AF: 0.000698

Gnomad NFE exome AF: 0.00671

Gnomad OTH exome AF: 0.0262

GnomAD4 exome AF: 0.0195 AC: 28489 AN: 1460720 Hom.: 2494 Cov.: 30 AF XY: 0.0196 AC XY: 14243 AN XY: 726704

African (AFR) AF: 0.349 AC: 11590 AN: 33184

American (AMR) AF: 0.0262 AC: 1171 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 280 AN: 26116

East Asian (EAS) AF: 0.0228 AC: 903 AN: 39658

South Asian (SAS) AF: 0.0568 AC: 4887 AN: 85988

European-Finnish (FIN) AF: 0.000712 AC: 38 AN: 53346

Middle Eastern (MID) AF: 0.0423 AC: 243 AN: 5742

European-Non Finnish (NFE) AF: 0.00639 AC: 7102 AN: 1111738

Other (OTH) AF: 0.0377 AC: 2275 AN: 60322

GnomAD4 genome AF: 0.106 AC: 16165 AN: 152230 Hom.: 2577 Cov.: 32 AF XY: 0.104 AC XY: 7723 AN XY: 74442

African (AFR) AF: 0.343 AC: 14231 AN: 41472

American (AMR) AF: 0.0458 AC: 701 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 47 AN: 3472

East Asian (EAS) AF: 0.0419 AC: 217 AN: 5182

South Asian (SAS) AF: 0.0729 AC: 352 AN: 4830

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10618

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00651 AC: 443 AN: 68036

Other (OTH) AF: 0.0753 AC: 159 AN: 2112

Alfa AF: 0.0144 Hom.: 124

Bravo AF: 0.118

TwinsUK AF: 0.00782 AC: 29

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.325 AC: 1212

ESP6500EA AF: 0.00829 AC: 68

ExAC AF: 0.0450 AC: 5438

Asia WGS AF: 0.106 AC: 368 AN: 3478

EpiCase AF: 0.00824

EpiControl AF: 0.00830

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	3.1
DANN	Benign	0.095
DEOGEN2	Benign	0.00040	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.039	T
MetaRNN	Benign	0.0077	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.96	N
PhyloP100		0.53
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.025
MPC		0.010
ClinPred		0.00014	T
GERP RS		2.5
Varity_R		0.056
gMVP		0.42
Mutation Taster		=98/2	polymorphism (auto)

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: rs6564956; hg19: chr16-82034435; COSMIC: COSV100200652;