8-115604876-G-C

Variant names:

• chr8-115604876-G-C
• NM_014112.5:c.1093C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014112.5(TRPS1):​c.1093C>G​(p.Gln365Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRPS1 NM_014112.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.56

Genes affected

TRPS1 (HGNC:12340): (transcriptional repressor GATA binding 1) This gene encodes a transcription factor that represses GATA-regulated genes and binds to a dynein light chain protein. Binding of the encoded protein to the dynein light chain protein affects binding to GATA consensus sequences and suppresses its transcriptional activity. Defects in this gene are a cause of tricho-rhino-phalangeal syndrome (TRPS) types I-III. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39943883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPS1	NM_014112.5	c.1093C>G	p.Gln365Glu	missense_variant	Exon 4 of 7	ENST00000395715.8	NP_054831.2
TRPS1	NM_001282903.3	c.1072C>G	p.Gln358Glu	missense_variant	Exon 4 of 7		NP_001269832.1
TRPS1	NM_001282902.3	c.1066C>G	p.Gln356Glu	missense_variant	Exon 3 of 6		NP_001269831.1
TRPS1	NM_001330599.2	c.1054C>G	p.Gln352Glu	missense_variant	Exon 3 of 6		NP_001317528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8	c.1093C>G	p.Gln365Glu	missense_variant	Exon 4 of 7	1	NM_014112.5	ENSP00000379065.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461800 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.;T;.;.;T;.
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;.;D;D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.40	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.;L;.;.;.;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.69	.;N;N;N;N;N;.
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	.;D;D;D;D;D;.
Sift4G	Pathogenic	0.0	.;D;D;D;D;D;D
Polyphen		0.98	D;D;D;.;D;.;.
Vest4		0.65, 0.67, 0.72, 0.63, 0.57
MutPred		0.33		Loss of helix (P = 0.0068);.;Loss of helix (P = 0.0068);.;.;Loss of helix (P = 0.0068);.;
MVP		0.39
MPC		0.22
ClinPred		0.88	D
GERP RS		5.7
Varity_R		0.46
gMVP		0.54

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: chr8-116617103;