16-84124638-T-G

Variant names:

• chr16-84124638-T-G
• NM_031463.5:c.985A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031463.5(HSDL1):​c.985A>C​(p.Thr329Pro) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HSDL1 NM_031463.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.439

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.072996765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSDL1	NM_031463.5	c.985A>C	p.Thr329Pro	missense_variant	Exon 6 of 6	ENST00000219439.9	NP_113651.4
HSDL1	NM_001146051.2	c.820A>C	p.Thr274Pro	missense_variant	Exon 7 of 7		NP_001139523.1
HSDL1	XM_005256189.4	c.985A>C	p.Thr329Pro	missense_variant	Exon 6 of 6		XP_005256246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSDL1	ENST00000219439.9	c.985A>C	p.Thr329Pro	missense_variant	Exon 6 of 6	1	NM_031463.5	ENSP00000219439.4
HSDL1	ENST00000434463.7	c.820A>C	p.Thr274Pro	missense_variant	Exon 7 of 7	2		ENSP00000407437.3
HSDL1	ENST00000619773.1	n.567A>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.985A>C (p.T329P) alteration is located in exon 6 (coding exon 4) of the HSDL1 gene. This alteration results from a A to C substitution at nucleotide position 985, causing the threonine (T) at amino acid position 329 to be replaced by a proline (P). 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	Benign	0.067
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.0079	T;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.39	T;T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.073	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.43	N;N
REVEL	Benign	0.18
Sift	Benign	0.052	T;T
Sift4G	Uncertain	0.059	T;T
Polyphen		0.0050	B;.
Vest4		0.10
MutPred		0.22		Loss of helix (P = 0.0167);.;
MVP		0.42
MPC		0.029
ClinPred		0.031	T
GERP RS		3.1
Varity_R		0.060
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-84158243;