Variant 11-71435795-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_001360.3(DHCR7):c.1008C>A(p.His336Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: not found (cov: 35)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DHCR7
NM_001360.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.957

Variant links:

Genes affected

DHCR7 (HGNC:2860): (7-dehydrocholesterol reductase) This gene encodes an enzyme that removes the C(7-8) double bond in the B ring of sterols and catalyzes the conversion of 7-dehydrocholesterol to cholesterol. This gene is ubiquitously expressed and its transmembrane protein localizes to the endoplasmic reticulum membrane and nuclear outer membrane. Mutations in this gene cause Smith-Lemli-Opitz syndrome (SLOS); a syndrome that is metabolically characterized by reduced serum cholesterol levels and elevated serum 7-dehydrocholesterol levels and phenotypically characterized by cognitive disability, facial dysmorphism, syndactyly of second and third toes, and holoprosencephaly in severe cases to minimal physical abnormalities and near-normal intelligence in mild cases. Alternative splicing results in multiple transcript variants that encode the same protein.[provided by RefSeq, Aug 2009]

DHCR7 links:

DHCR7 (HGNC:):

DHCR7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a transmembrane_region Helical (size 20) in uniprot entity DHCR7_HUMAN there are 8 pathogenic changes around while only 0 benign (100%) in NM_001360.3

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30128467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHCR7	NM_001360.3 linkuse as main transcript	c.1008C>A	p.His336Gln	missense_variant	9/9	ENST00000355527.8	NP_001351.2	Q9UBM7A0A024R5F7
DHCR7	NM_001163817.2 linkuse as main transcript	c.1008C>A	p.His336Gln	missense_variant	9/9		NP_001157289.1	Q9UBM7A0A024R5F7
DHCR7	XM_011544777.3 linkuse as main transcript	c.1142C>A	p.Thr381Lys	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHCR7	ENST00000355527.8 linkuse as main transcript	c.1008C>A	p.His336Gln	missense_variant	9/9	1	NM_001360.3	ENSP00000347717.4		Q9UBM7
DHCR7	ENST00000685320.1 linkuse as main transcript	c.423C>A	p.His141Gln	missense_variant	8/8			ENSP00000509319.1		B4E1K5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000409

AC:

AN:

244518

Hom.:

AF XY:

0.00000749

AC XY:

AN XY:

133452

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455548

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723120

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.040

BayesDel_noAF

Benign

-0.10

CADD

Benign

0.0040

DANN

Benign

0.21

DEOGEN2

Uncertain

0.79

D;D;D

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.82

.;T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.30

T;T;T

MetaSVM

Uncertain

0.74

MutationAssessor

Benign

1.3

L;L;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.8

N;N;N

REVEL

Uncertain

0.46

Sift

Benign

0.27

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.60

P;P;.

Vest4

0.22

MutPred

0.36

Gain of catalytic residue at H336 (P = 0.063);Gain of catalytic residue at H336 (P = 0.063);.;

MVP

0.78

MPC

0.29

ClinPred

0.17

GERP RS

-8.1

Varity_R

0.047

gMVP

0.79

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over