8-115587144-G-C

Variant names:

• chr8-115587144-G-C
• NM_014112.5:c.2557C>G

Variant summary

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

The NM_014112.5(TRPS1):​c.2557C>G​(p.Arg853Gly) 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 1,461,852 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRPS1 NM_014112.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25256458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPS1	NM_014112.5	c.2557C>G	p.Arg853Gly	missense_variant	Exon 5 of 7	ENST00000395715.8	NP_054831.2
TRPS1	NM_001282903.3	c.2536C>G	p.Arg846Gly	missense_variant	Exon 5 of 7		NP_001269832.1
TRPS1	NM_001282902.3	c.2530C>G	p.Arg844Gly	missense_variant	Exon 4 of 6		NP_001269831.1
TRPS1	NM_001330599.2	c.2518C>G	p.Arg840Gly	missense_variant	Exon 4 of 6		NP_001317528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8	c.2557C>G	p.Arg853Gly	missense_variant	Exon 5 of 7	1	NM_014112.5	ENSP00000379065.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461852 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727236

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.40
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T;.;T;.;.;T;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.95	D;D;.;D;D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.25	T;T;T;T;T;T;T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	0.69	N;.;N;.;.;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.75	.;N;N;N;N;N;.
REVEL	Uncertain	0.56
Sift	Pathogenic	0.0	.;D;D;D;D;D;.
Sift4G	Uncertain	0.055	.;T;T;T;T;T;T
Polyphen		0.022	B;B;B;.;B;.;.
Vest4		0.88, 0.93, 0.90, 0.87, 0.84
MutPred		0.61		Gain of catalytic residue at A839 (P = 0.0324);.;Gain of catalytic residue at A839 (P = 0.0324);.;.;Gain of catalytic residue at A839 (P = 0.0324);.;
MVP		0.98
MPC		1.0
ClinPred		0.37	T
GERP RS		1.6
Varity_R		0.31
gMVP		0.37

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: chr8-116599371;