9-112454063-C-G

Variant names:

• chr9-112454063-C-G
• rs200143255
• NM_032303.5:c.916C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032303.5(HSDL2):​c.916C>G​(p.Arg306Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. R306C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HSDL2 NM_032303.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• Publications: 0 publications found

Genes affected

HSDL2 (HGNC:18572): (hydroxysteroid dehydrogenase like 2) Predicted to enable oxidoreductase activity. Located in mitochondrion and peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

HSDL2-AS1 (HGNC:31438): (HSDL2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06314188).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032303.5. 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
	HSDL2	NM_032303.5	MANE Select	c.916C>G	p.Arg306Gly	missense	Exon 9 of 11	NP_115679.2
	HSDL2	NM_001195822.2		c.697C>G	p.Arg233Gly	missense	Exon 7 of 9	NP_001182751.1	Q6YN16-2
	HSDL2	NR_036651.2		n.808C>G		non_coding_transcript_exon	Exon 8 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSDL2	ENST00000398805.8	TSL:1 MANE Select	c.916C>G	p.Arg306Gly	missense	Exon 9 of 11	ENSP00000381785.3	Q6YN16-1
	HSDL2	ENST00000398803.1	TSL:1	c.697C>G	p.Arg233Gly	missense	Exon 7 of 9	ENSP00000381783.1	Q6YN16-2
	HSDL2	ENST00000942135.1		c.910C>G	p.Arg304Gly	missense	Exon 9 of 11	ENSP00000612194.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461482 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727062

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111696

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.7
DANN	Benign	0.89
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.21
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.64	N
REVEL	Benign	0.020
Sift	Benign	0.43	T
Sift4G	Benign	0.48	T
Polyphen		0.0	B
Vest4		0.075
MutPred		0.25		Loss of loop (P = 0.0112)
MVP		0.44
MPC		0.19
ClinPred		0.047	T
GERP RS		1.4
Varity_R		0.058
gMVP		0.39
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs200143255; hg19: chr9-115216343;