rs2086646516

Variant names:

• chr16-84130010-C-G
• rs2086646516
• NM_031463.5:c.642G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-84130010-C-G
• chr16-84130010-C-T

Variant summary

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

The NM_031463.5(HSDL1):​c.642G>C​(p.Gln214His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSDL1 NM_031463.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.402
• Publications: 0 publications found

Genes affected

HSDL1 (HGNC:16475): (hydroxysteroid dehydrogenase like 1) Predicted to enable oxidoreductase activity. Located in intermediate filament cytoskeleton and mitochondrion. [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=0.22588217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSDL1	NM_031463.5	c.642G>C	p.Gln214His	missense_variant	Exon 4 of 6	ENST00000219439.9	NP_113651.4
HSDL1	NM_001146051.2	c.477G>C	p.Gln159His	missense_variant	Exon 5 of 7		NP_001139523.1
HSDL1	XM_005256189.4	c.642G>C	p.Gln214His	missense_variant	Exon 4 of 6		XP_005256246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSDL1	ENST00000219439.9	c.642G>C	p.Gln214His	missense_variant	Exon 4 of 6	1	NM_031463.5	ENSP00000219439.4
HSDL1	ENST00000434463.7	c.477G>C	p.Gln159His	missense_variant	Exon 5 of 7	2		ENSP00000407437.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.642G>C (p.Q214H) alteration is located in exon 4 (coding exon 2) of the HSDL1 gene. This alteration results from a G to C substitution at nucleotide position 642, causing the glutamine (Q) at amino acid position 214 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.85
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.36	N;.
PhyloP100		0.40
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.20
Sift	Benign	0.54	T;T
Sift4G	Benign	0.54	T;T
Polyphen		0.0010	B;.
Vest4		0.27
MutPred		0.57		Gain of glycosylation at T212 (P = 0.0703);.;
MVP		0.69
MPC		0.025
ClinPred		0.14	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.084
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2086646516; hg19: chr16-84163615;