1-152972053-C-T

Variant names:

• chr1-152972053-C-T
• NM_173080.3:c.163C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173080.3(SPRR4):​c.163C>T​(p.Pro55Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: SPRR4 NM_173080.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.211

Genes affected

SPRR4 (HGNC:23173): (small proline rich protein 4) Predicted to be involved in keratinization. Predicted to be located in cell cortex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046810538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRR4	NM_173080.3	c.163C>T	p.Pro55Ser	missense_variant	Exon 2 of 2	ENST00000328051.3	NP_775103.1
SPRR4	XM_017000482.3	c.163C>T	p.Pro55Ser	missense_variant	Exon 3 of 3		XP_016855971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRR4	ENST00000328051.3	c.163C>T	p.Pro55Ser	missense_variant	Exon 2 of 2	1	NM_173080.3	ENSP00000332163.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000662

GnomAD4 genome Cov.: 31

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 31, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.163C>T (p.P55S) alteration is located in exon 2 (coding exon 1) of the SPRR4 gene. This alteration results from a C to T substitution at nucleotide position 163, causing the proline (P) at amino acid position 55 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.3
DANN	Benign	0.57
DEOGEN2	Benign	0.054	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.92	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.097
Sift	Benign	0.13	T
Sift4G	Benign	0.11	T
Polyphen		0.0060	B
Vest4		0.13
MutPred		0.10		Loss of catalytic residue at P55 (P = 2e-04);
MVP		0.093
MPC		0.0039
ClinPred		0.12	T
GERP RS		0.57
Varity_R		0.068
gMVP		0.0046

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-152944529;