1-153040250-G-T

Variant names:

• chr1-153040250-G-T
• rs186214884
• NM_006945.5:c.97C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006945.5(SPRR2D):​c.97C>A​(p.Pro33Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P33S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SPRR2D NM_006945.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.432
• Publications: 0 publications found

Genes affected

SPRR2D (HGNC:11264): (small proline rich protein 2D) Predicted to be involved in keratinization. Predicted to act upstream of or within female gonad development and response to estradiol. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10282186).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006945.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRR2D	NM_006945.5	MANE Select	c.97C>A	p.Pro33Thr	missense	Exon 2 of 2	NP_008876.3
	SPRR2D	NM_001382248.1		c.97C>A	p.Pro33Thr	missense	Exon 2 of 2	NP_001369177.1	P22532

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRR2D	ENST00000360379.4	TSL:1 MANE Select	c.97C>A	p.Pro33Thr	missense	Exon 2 of 2	ENSP00000353542.3	P22532
	SPRR2D	ENST00000368756.1	TSL:2	c.97C>A	p.Pro33Thr	missense	Exon 3 of 3	ENSP00000357745.1	P22532
	SPRR2D	ENST00000368757.1	TSL:3	c.97C>A	p.Pro33Thr	missense	Exon 2 of 2	ENSP00000357746.1	P22532

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460330 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726476

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4660

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111818

Other (OTH) AF: 0.00 AC: 0 AN: 60268

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	3.5
DANN	Benign	0.37
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.43
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.12
Sift4G	Uncertain	0.022	D
Polyphen		0.25	B
Vest4		0.27
MutPred		0.11		Gain of phosphorylation at P33 (P = 0.0187)
MVP		0.32
MPC		0.53
ClinPred		0.15	T
GERP RS		-0.62
Varity_R		0.57
gMVP		0.0035
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs186214884; hg19: chr1-153012726;