rs370923206

Variant names:

• chr17-42190848-C-G
• rs370923206
• NM_032484.5:c.1138G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-42190848-C-G
• chr17-42190848-C-T

Variant summary

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

The NM_032484.5(GHDC):​c.1138G>C​(p.Val380Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,226 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/20 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. V380I) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: GHDC NM_032484.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22

Genes affected

GHDC (HGNC:24438): (GH3 domain containing) Predicted to enable acid-amino acid ligase activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHDC	NM_032484.5	c.1138G>C	p.Val380Leu	missense_variant	Exon 7 of 10	ENST00000587427.6	NP_115873.1
GHDC	NM_001142623.2	c.1138G>C	p.Val380Leu	missense_variant	Exon 7 of 10		NP_001136095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHDC	ENST00000587427.6	c.1138G>C	p.Val380Leu	missense_variant	Exon 7 of 10	1	NM_032484.5	ENSP00000467585.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74364

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.0033	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.041	.;T;.;T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.81	T;.;.;T;T
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.68	D;D;D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.8	.;L;L;L;L
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.9	.;N;N;.;.
REVEL	Benign	0.20
Sift	Benign	0.067	.;T;T;.;.
Sift4G	Benign	0.10	T;T;T;T;T
Polyphen		1.0, 0.57	.;D;P;D;P
Vest4		0.61
MutPred		0.49		Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);
MVP		0.11
MPC		0.64
ClinPred		0.87	D
GERP RS		3.2
Varity_R		0.075
gMVP		0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs370923206; hg19: chr17-40342866;