16-84130150-C-A

Variant names:

• chr16-84130150-C-A
• rs776186248
• NM_031463.5:c.502G>T

Variant summary

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

The NM_031463.5(HSDL1):​c.502G>T​(p.Asp168Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D168N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSDL1 NM_031463.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031463.5. 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
	HSDL1	NM_031463.5	MANE Select	c.502G>T	p.Asp168Tyr	missense	Exon 4 of 6	NP_113651.4
	HSDL1	NM_001146051.2		c.337G>T	p.Asp113Tyr	missense	Exon 5 of 7	NP_001139523.1	Q3SXM5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSDL1	ENST00000219439.9	TSL:1 MANE Select	c.502G>T	p.Asp168Tyr	missense	Exon 4 of 6	ENSP00000219439.4	Q3SXM5-1
	HSDL1	ENST00000934215.1		c.502G>T	p.Asp168Tyr	missense	Exon 3 of 5	ENSP00000604274.1
	HSDL1	ENST00000934216.1		c.502G>T	p.Asp168Tyr	missense	Exon 5 of 7	ENSP00000604275.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Pathogenic	0.81	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		2.2
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.016	D
Polyphen		0.30	B
Vest4		0.60
MutPred		0.49		Loss of ubiquitination at K169 (P = 0.0896)
MVP		0.90
MPC		0.16
ClinPred		0.97	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.79
gMVP		0.82

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: rs776186248; hg19: chr16-84163755;