NM_031463.5:c.985A>C

Variant names:

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

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.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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HSDL1 NM_031463.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.439
• 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=0.072996765).

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.985A>C	p.Thr329Pro	missense	Exon 6 of 6	NP_113651.4
	HSDL1	NM_001146051.2		c.820A>C	p.Thr274Pro	missense	Exon 7 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.985A>C	p.Thr329Pro	missense	Exon 6 of 6	ENSP00000219439.4	Q3SXM5-1
	HSDL1	ENST00000934215.1		c.985A>C	p.Thr329Pro	missense	Exon 5 of 5	ENSP00000604274.1
	HSDL1	ENST00000934216.1		c.985A>C	p.Thr329Pro	missense	Exon 7 of 7	ENSP00000604275.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.44
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.18
Sift	Benign	0.052	T
Sift4G	Uncertain	0.059	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

Other links and lift over

hg19: chr16-84158243;