NM_001004353.4:c.376A>G

Variant names:

• chr9-137252108-A-G
• rs28657439
• NM_001004353.4:c.376A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001004353.4(STPG3):​c.376A>G​(p.Ser126Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,611,880 control chromosomes in the GnomAD database, including 220 homozygotes. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0093 (9 hom., cov: 32)
  • Exomes 𝑓: 0.015 (211 hom.)
• Consequence: STPG3 NM_001004353.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.115
• Publications: 7 publications found

Genes affected

STPG3 (HGNC:37285): (sperm-tail PG-rich repeat containing 3) Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

CIMIP2A (HGNC:33818): (ciliary microtubule inner protein 2A) Located in ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

STPG3-AS1 (HGNC:51176): (STPG3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034903288).
• BP6: Variant 9-137252108-A-G is Benign according to our data. Variant chr9-137252108-A-G is described in ClinVar as Benign. ClinVar VariationId is 774890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0149 (21797/1459600) while in subpopulation NFE AF = 0.0184 (20436/1111580). AF 95% confidence interval is 0.0182. There are 211 homozygotes in GnomAdExome4. There are 10544 alleles in the male GnomAdExome4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004353.4. 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
	STPG3	NM_001004353.4	MANE Select	c.376A>G	p.Ser126Gly	missense	Exon 3 of 6	NP_001004353.2	Q8N7X2-4
	STPG3	NM_001256699.2		c.376A>G	p.Ser126Gly	missense	Exon 3 of 6	NP_001243628.1	Q8N7X2-2
	STPG3	NM_001256700.2		c.376A>G	p.Ser126Gly	missense	Exon 3 of 6	NP_001243629.1	Q8N7X2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STPG3	ENST00000412566.6	TSL:1 MANE Select	c.376A>G	p.Ser126Gly	missense	Exon 3 of 6	ENSP00000391218.1	Q8N7X2-4
	STPG3	ENST00000388931.7	TSL:1	c.376A>G	p.Ser126Gly	missense	Exon 3 of 6	ENSP00000373583.3	Q8N7X2-2
	STPG3	ENST00000611378.4	TSL:1	c.376A>G	p.Ser126Gly	missense	Exon 3 of 6	ENSP00000477998.1	Q8N7X2-3

Frequencies

GnomAD3 genomes AF: 0.00930 AC: 1415 AN: 152162 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00350

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0155

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00861 AC: 2124 AN: 246648 AF XY: 0.00879

Gnomad AFR exome AF: 0.00318

Gnomad AMR exome AF: 0.00480

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.000335

Gnomad FIN exome AF: 0.00306

Gnomad NFE exome AF: 0.0154

Gnomad OTH exome AF: 0.00868

GnomAD4 exome AF: 0.0149 AC: 21797 AN: 1459600 Hom.: 211 Cov.: 34 AF XY: 0.0145 AC XY: 10544 AN XY: 726096

African (AFR) AF: 0.00200 AC: 67 AN: 33480

American (AMR) AF: 0.00466 AC: 208 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.000268 AC: 7 AN: 26100

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39698

South Asian (SAS) AF: 0.00226 AC: 195 AN: 86206

European-Finnish (FIN) AF: 0.00409 AC: 212 AN: 51778

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5750

European-Non Finnish (NFE) AF: 0.0184 AC: 20436 AN: 1111580

Other (OTH) AF: 0.0109 AC: 659 AN: 60342

GnomAD4 genome AF: 0.00930 AC: 1416 AN: 152280 Hom.: 9 Cov.: 32 AF XY: 0.00862 AC XY: 642 AN XY: 74452

African (AFR) AF: 0.00349 AC: 145 AN: 41550

American (AMR) AF: 0.00588 AC: 90 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4828

European-Finnish (FIN) AF: 0.00273 AC: 29 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0155 AC: 1057 AN: 68006

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.0137 Hom.: 56

Bravo AF: 0.00964

TwinsUK AF: 0.0181 AC: 67

ALSPAC AF: 0.0187 AC: 72

ESP6500AA AF: 0.00223 AC: 9

ESP6500EA AF: 0.0155 AC: 129

ExAC AF: 0.00877 AC: 1061

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0131

EpiControl AF: 0.0126

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Uncertain	0.97
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.12
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.11
Sift	Benign	0.20	T
Sift4G	Uncertain	0.0090	D
Polyphen		0.77	P
Vest4		0.35
MVP		0.49
MPC		0.096
ClinPred		0.029	T
GERP RS		3.8
Varity_R		0.14
gMVP		0.56
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: rs28657439; hg19: chr9-140146560; COSMIC: COSV100547149; COSMIC: COSV100547149;