1-152972083-C-G

Variant names:

• chr1-152972083-C-G
• NM_173080.3:c.193C>G

Variant summary

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

The NM_173080.3(SPRR4):​c.193C>G​(p.Gln65Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 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)
• Consequence: SPRR4 NM_173080.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.765

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=0.055494428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRR4	NM_173080.3	c.193C>G	p.Gln65Glu	missense_variant	Exon 2 of 2	ENST00000328051.3	NP_775103.1
SPRR4	XM_017000482.3	c.193C>G	p.Gln65Glu	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.193C>G	p.Gln65Glu	missense_variant	Exon 2 of 2	1	NM_173080.3	ENSP00000332163.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.193C>G (p.Q65E) alteration is located in exon 2 (coding exon 1) of the SPRR4 gene. This alteration results from a C to G substitution at nucleotide position 193, causing the glutamine (Q) at amino acid position 65 to be replaced by a glutamic acid (E). 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	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.91	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.021
Sift	Benign	0.17	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.21
MutPred		0.11		Gain of ubiquitination at K66 (P = 0.0185);
MVP		0.11
MPC		0.0037
ClinPred		0.11	T
GERP RS		3.2
Varity_R		0.072
gMVP		0.0015

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: chr1-152944559;