chr1-3627583-A-C

Position:

• chr1-3627583-A-C

Variant summary

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

The NM_182752.4(TPRG1L):​c.554A>C​(p.Asn185Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TPRG1L NM_182752.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93

Genes affected

TPRG1L (HGNC:27007): (tumor protein p63 regulated 1 like) Predicted to enable identical protein binding activity. Predicted to be involved in regulation of glutamatergic synaptic transmission. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

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=0.16082823).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPRG1L	NM_182752.4	c.554A>C	p.Asn185Thr	missense_variant	4/5	ENST00000378344.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPRG1L	ENST00000378344.7	c.554A>C	p.Asn185Thr	missense_variant	4/5	2	NM_182752.4	P1
TPRG1L	ENST00000344579.5	c.377A>C	p.Asn126Thr	missense_variant	3/4	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461746 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727166

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.085	T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.15	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.053
Sift	Benign	0.17	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.044	B;B
Vest4		0.51
MutPred		0.28		Gain of glycosylation at N185 (P = 0.0362);.;
MVP		0.15
MPC		0.29
ClinPred		0.54	D
GERP RS		1.2
Varity_R		0.081
gMVP		0.36

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: rs1203957797; hg19: chr1-3544147;